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  • 1.
    Botling, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Immune Biomarkers on the Radar-Comprehensive "Immunograms" for Multimodal Treatment Prediction2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 5, p. 770-772Article in journal (Other academic)
  • 2.
    Dietel, M.
    et al.
    Charite Berlin Mitte, Inst Pathol, Berlin, Germany.
    Savelov, N.
    Moscow Oncol Hosp, Moscow, Russia.
    Salanova, R.
    Hosp Gastroenterol Dr Carlos Bonorino Udaondo, Buenos Aires, DF, Argentina.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Bigras, G.
    Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada.
    Hida, T.
    Aichi Canc Ctr, Dept Thorac Oncol, Nagoya, Aichi, Japan.
    Piperdi, B.
    Merck & Co Inc, Kenilworth, NJ USA.
    Burke, T.
    Merck & Co Inc, Kenilworth, NJ USA.
    Khambata-Ford, S.
    Merck & Co Inc, Kenilworth, NJ USA.
    Deitz, A.
    Merck & Co Inc, Kenilworth, NJ USA.
    30O Real-world prevalence of PD-L1 expression in locally advanced or metastatic non-small cell lung cancer (NSCLC): The global, multicentre EXPRESS study2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 4, p. S74-S75Article in journal (Other academic)
  • 3.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Grinberg, Marianna
    Tu Dortmund Univ, Dept Stat, Dortmund, Germany..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Edlund, Karolina
    Tu Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Rahnenfuehrer, Joerg
    Tu Dortmund Univ, Dept Stat, Dortmund, Germany..
    Hengstler, Jan
    Tu Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Brunnström, Hans
    Lund Univ, Div Pathol, Lund, Sweden..
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Pneumol, Gavle, Sweden..
    Branden, Eva
    Gavle Cent Hosp, Dept Pneumol, Gavle, Sweden..
    Lambe, Mats
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden..
    Jirström, Karin
    Lund Univ, Div Pathol, Lund, Sweden..
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Micke, Patrick
    The Crux of Molecular Prognostications in NSCLC: An Optimized Biomarker Panel Fails to Outperform Clinical Parameters2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S712-S713Article in journal (Other academic)
  • 4.
    Djureinovic, Dijana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hallström, Björn
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Fagerberg, Linn
    Brunnström, Hans
    Lund Univ, Div Pathol, Lund, Sweden..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Pneumol, S-80187 Gavle, Sweden..
    Lambe, Mats
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden..
    Branden, Eva
    Gavle Cent Hosp, Dept Pneumol, S-80187 Gavle, Sweden..
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Uhlen, Mathias
    Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    The Identification of Therapeutic Targets in Lung Cancer Based on Transcriptomic and Proteomic Characterization of Cancer-Testis Antigens2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S256-S256Article in journal (Other academic)
  • 5.
    Edlund, Karolina
    et al.
    TU Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany.
    Madjar, Katrin
    TU Dortmund Univ, Dept Stat, Dortmund, Germany.
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Djureinovic, Dijana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Brunnström, Hans
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gävle Cent Hosp, Dept Resp Med, Gävle, Sweden.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gävle Cent Hosp, Dept Resp Med, Gävle, Sweden.
    Jirström, Karin
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Rahnenführer, Jörg
    TU Dortmund Univ, Dept Stat, Dortmund, Germany.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hengstler, Jan G
    TU Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany.
    Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC2019In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 14, no 4, p. 628-640, article id S1556-0864(19)30009-7Article in journal (Refereed)
    Abstract [en]

    Introduction: Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this has not been thoroughly investigated in relation to the expression of programmed death ligand 1 (PD-L1). Here, we determine the association of lymphocytes and PD-L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients who were not treated with checkpoint inhibitors targeting the programmed death 1/PD-L1 axis. Moreover, we evaluate how PD-L1 positivity and clinicopathologic factors affect the prognostic association of lymphocytes.

    Methods: Cluster of differentiation (CD) 3 (CD3)-, CD8-, CD4-, forkhead box P3 (FOXP3)-, CD20-, CD79A-, and immunoglobulin kappa constant (IGKC)-positive immune cells, and tumor PD-L1 positivity, were determined by immunohistochemistry on tissue microarrays (n = 705). Affymetrix data was analyzed for a patient subset, and supplemented with publicly available transcriptomics data (N = 1724). Associations with OS were assessed by Kaplan-Meier plots and uni- and multivariate Cox regression.

    Results: Higher levels of T and B plasma cells were associated with longer OS (p = 0.004 and p < 0.001, for CD8 and IGKC, respectively). Highly proliferative tumors with few lymphocytes had the worst outcome. No association of PD-L1 positivity with OS was observed in a nonstratified patient population; however, a significant association with shorter OS was observed in never-smokers (p = 0.009 and p = 0.002, 5% and 50% cutoff). Lymphocyte infiltration was not associated with OS in PD-L1–positive tumors (50% cutoff). The prognostic association of lymphocyte infiltration also depended on the patients’ smoking history and histologic subtype.

    Conclusions: Proliferation, PD-L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.

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  • 6.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Overview of Current International Randomized Trials2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S108-S108Article in journal (Other academic)
  • 7.
    Ekman, Simon
    et al.
    Karolinska Univ Hosp, Oncol, Stockholm, Sweden.
    Sorensen, Jens Benn
    Rigshosp Blegdamsvej, Copenhagen O, Denmark.
    Rockberg, Julia
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Daumont, Melinda
    Bristol Myers Squibb, Rueil Malmaison, France.
    Sobocki, Patrik
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Klint, Peter
    Bristol Myers Squibb, Solna, Sweden.
    Huang, Han-Yao
    Bristol Myers Squibb, Pennington, NJ USA.
    Svard, Jenny
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Chirita, Oana
    Bristol Myers Squibb, Uxbridge, Middx, England.
    Jorgensen, Leif
    Pygargus Ab, Ims Hlth Sweden, Rwes, Solna, Sweden.
    Planck, Maria
    Lund Univ, Oncol & Pathol, Lund, Sweden.
    Overall Survival and Intermediate Outcomes among Scandinavian Non-Small Cell Lung Cancer Patients: The SCAN-LEAF Study2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S6391-S6391Article in journal (Other academic)
  • 8.
    Granberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fazio, Nicola
    Grossman, Ashley
    Saletan, Stephen
    Pannnerselvam, Ashok
    Wolin, Edward
    Everolimus Plus Octreotide Lar in Patients with Lung Carcinoids2014In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 9, no 9, p. S179-S179Article in journal (Refereed)
  • 9.
    Gulyas, Miklos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Mattsson, Johanna S. M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lindgren, Andrea
    Linkoping Univ, Inst Med & Hlth, Linkoping, Sweden..
    Sederholm, Christer
    Linkoping Univ Hosp, Pulm Med, S-58185 Linkoping, Sweden..
    Ek, Lars
    Skane Univ Hosp, Pulm Med, Lund, Sweden..
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Behndig, Annelie
    Norrland Univ Hosp, Pulm Med, Umea, Sweden..
    Holmberg, Erik
    Univ Gothenburg, Inst Clin Sci, Sahlgrensk Acad, Dept Oncol, Gothenburg, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergman, Bengt
    Sahlgrens Univ Hosp, Dept Pulm Med, Gothenburg, Sweden..
    COX-2 Expression Does Not Predict Outcome of Celecoxib in Addition to Standard Chemotherapy in Advanced Non-Small Cell Lung Cancer2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S541-S542Article in journal (Other academic)
  • 10.
    Isaksson, Johan
    et al.
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Willen, Linda
    Gavle Cent Hosp, Dept Oncol, Gavle, Sweden.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mindus, Stephanie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Branden, Eva
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Moens, Lotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Lundberg, Gabriel
    Falun Cty Hosp, Dept Resp Med, Falun, Sweden.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Establishing Reflex NGS Testing in NSCLC in a Regional Network of County Hospitals in Central Sweden2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S499-S500Article in journal (Other academic)
  • 11.
    Karlsson, Anna
    et al.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden..
    Brunnström, Hans
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.;Reg Labs Reg Skane, Dept Pathol, Lund, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Veerla, Srinivas
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden..
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Jönsson, Mats
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden..
    Reuterswärd, Christel
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden..
    Planck, Maria
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden.;Skane Univ Hosp, Dept Resp Med & Allergol, Lund, Sweden..
    Staaf, Johan
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22381 Lund, Sweden..
    Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 8, p. 1257-1267Article in journal (Refereed)
    Abstract [en]

    Introduction: Large cell lung cancer (LCLC) and large cell neuroendocrine carcinoma (LCNEC) constitute a small proportion of NSCLC. The WHO 2015 classification guidelines changed the definition of the debated histological subtype LCLC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine whether these new guidelines also translate into the transcriptional landscape of lung cancer, and LCLC specifically.

    Methods: Gene expression profiling was performed by using Illumina V4 HT12 microarrays (Illumina, San Diego, CA) on samples from 159 cases (comprising all histological subtypes, including 10 classified as LCLC WHO 2015 and 14 classified as LCNEC according to the WHO 2015 guidelines), with complimentary mutational and immunohistochemical data. Derived transcriptional phenotypes were validated in 199 independent tumors, including six WHO 2015 LCLCs and five LCNECs.

    Results: Unsupervised analysis of gene expression data identified a phenotype comprising 90% of WHO 2015 LCLC tumors, with characteristics of poorly differentiated proliferatiVe cancer, a 90% tumor protein p53 gene (TP53) mutation rate, and lack of well-known NSCLC oncogene driver alterations. Validation in independent data confirmed aggregation of WHO 2015 LCLCs in the specific phenotype. For LCNEC tumors, the unsupervised gene expression analysis suggested two different transcriptional patterns corresponding to a proposed genetic division of LCNEC tumors into SCLC-like and NSCLC-like cancer on the basis of TP53 and retinoblastoma 1 gene (RB1) alteration patterns.

    Conclusions: Refined classification of LCLC has implications for diagnosis, prognostics, and therapy decisions. Our molecular analyses support the WHO 2015 classification of LCLC and LCNEC tumors, which herein follow different tumorigenic paths and can accordingly be stratified into different transcriptional subgroups, thus linking diagnostic immunohistochemical staining driven classification with the transcriptional landscape of lung cancer.

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  • 12.
    Kerr, K.
    et al.
    Univ Aberdeen, Med Sch, Aberdeen Royal Infirm, Aberdeen, Scotland.
    Tsao, M.
    Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada;Univ Toronto, Toronto, ON, Canada.
    Yatabe, Y.
    Aichi Canc Ctr, Nagoya, Aichi, Japan.
    Thunnissen, E.
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
    Nicholson, A.
    Imperial Coll London, Royal Brompton, London, England.
    Moreira, A.
    New York Univ Langone Hlth, New York, NY USA.
    Chou, T.
    Taipei Vet Gen Hosp, Taipei, Taiwan.
    Borczuk, A.
    Weill Cornell Med, New York, NY USA.
    Bubendorf, L.
    Universiteitsspital Basel, Pathol, Basel, Switzerland.
    Mino-Kenudson, M.
    Massachusetts Gen Hosp, Boston, MA 02114 USA;Harvard Med Sch, Boston, MA 02114 USA.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Beasley, M. B.
    Mt Sinai Med Ctr, New York, NY 10029 USA.
    Chirieac, L.
    Harvard Med Sch, Boston, MA 02114 USA;Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
    Dacic, S.
    Univ Pittsburgh, Pittsburgh, PA USA.
    Lantuejoul, S.
    Ctr Leon Berard, Lyon, France.
    Pelosi, G.
    Univ Milan, Milan, Italy;IRCCS Multimedia, Interhosp Pathol Div, Milan, Italy.
    Chung, J.
    Seoul Natl Univ, Bundang Hosp, Seoul, South Korea.
    Chen, G.
    Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China.
    Russell, P.
    St Vincents Pathol, Fitzroy, Vic, Australia.
    Poleri, C.
    Consultorio Patol Especializada, Buenos Aires, DF, Argentina.
    Sauter, J.
    Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
    Yu, H.
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA.
    Noguchi, M.
    Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan.
    Wistuba, I.
    MD Anderson Canc Ctr, Houston, TX USA.
    Pintilie, M.
    Princess Margaret Canc Ctr, Toronto, ON, Canada.
    Wynes, M.
    lnt Assoc Study Lung Canc, Aurora, CO USA.
    Hirsch, F.
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA.
    Phase 2B of Blueprint PD-L1 Immunohistochemistry Assay Comparability Study2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 10, p. S325-S325Article in journal (Other academic)
  • 13. Kerr, Keith M
    et al.
    Tsao, Ming-Sound
    Nicholson, Andrew G
    Yatabe, Yasushi
    Wistuba, Ignacio I
    Hirsch, Fred R
    Botling, Johan
    IASLC Pathology Committee.
    Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer: In what state is this art?2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 7, p. 985-989Article in journal (Refereed)
    Abstract [en]

    Therapeutic antibodies to programmed death receptor 1 (PD-1) and its ligand PD-L1 show promising clinical results. Anti-PD-L1 immunohistochemistry (IHC) may be a biomarker to select patients more likely to respond to these treatments. However, the development of at least four different therapeutics, each with a different anti-PD-L1 IHC assay, has raised concerns among pathologists and oncologists alike. This article reviews existing data on the IHC biomarker aspects of studies using these drugs in non-small-cell lung cancer (NSCLC) and considers the challenges ahead, should these drug/IHC assay combinations reach routine practice. For each the known biomarker assays in development, there is a different monoclonal IHC antibody clone, produced by one of two diagnostics companies. Each test requires proprietary staining platforms and uses different definitions of a "positive" test for PD-L1 expression, on tumor cells and, in one test, also on tumor infiltrating immune cells. There are still considerable gaps in our knowledge of the technical aspects of these tests, and of the biological implications and associations of PD-L1 expression in NSCLC, considering heterogeneity of expression, dynamic changes in expression, and prognostic implications among other factors. The International Association for the Study of Lung Cancer Pathology Committee raises the prospect of trying not only to harmonize and standardize testing for PD-L1 by IHC, at least at a technical level, but also, ideally, as a predictive marker, to facilitate availability of this test and a promising treatment for patients with NSCLC.

  • 14.
    Koyi, Hirsh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Hillerdal, Gunnar
    Treatment of Elderly (70 Years or Older) with Lung Cancer. A Four-Year Material in Clinical Practice from Karolinska University Hospital - Sweden2013In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 8, p. S401-S401Article in journal (Other academic)
  • 15.
    Koyi, Hirsh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Hillerdal, Gunnar
    Andersson, Olov
    Högberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Lung Cancer Among Swedish and Imigrants. Incidens, Histopathology, Treatment and Survival2013In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 8, no S2, p. S881-S881Article in journal (Other academic)
  • 16.
    Koyi, Hirsh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Hillerdal, Gunnar
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Treatment of Elderly Patients (< 70 Years) with Non-Small Cell Lung Cancer Given Chemotherapy. A Four-Year Material in Clinical Practice from Karolinska University Hospital Sweden2013In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 8, p. S402-S402Article in journal (Other academic)
  • 17.
    Koyi, Hirsh
    et al.
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Hillerdal, Gunnar
    Karolinska Univ Hosp, Dept Resp Med, Stockholm, Sweden..
    Friesland, Signe
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Kolbeck, Karl Gustav
    Karolinska Univ Hosp, Dept Resp Med, Stockholm, Sweden..
    Andersson, Olov
    Karolinska Univ Hosp, Dept Resp Med, Stockholm, Sweden..
    Bergman, Per
    Karolinska Univ Hosp, Dept Thorac Surg, Stockholm, Sweden..
    Orre, Lotta
    Karolinska Univ Hosp, Dept Thorac Surg, Stockholm, Sweden..
    Liv, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Branden, Eva
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Stereotactic Body Radiotherapy (SBRT) or Surgery in Early Stage (I & II) Non Small Cell Lung Cancer (NSCLC)2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S566-S566Article in journal (Other academic)
  • 18.
    Koyi, Hirsh
    et al.
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Hillerdal, Gunnar
    Karolinska Univ Hosp, Deartment Resp Med, Stockholm, Sweden..
    Kolbeck, Karl Gustav
    Karolinska Univ Hosp, Deartment Resp Med, Stockholm, Sweden..
    Andersson, Olov
    Karolinska Univ Hosp, Deartment Resp Med, Stockholm, Sweden..
    Bergman, Per
    Karolinska Univ Hopsital, Deprtment Thorac Surg, Stockholm, Sweden..
    Orre, Lotta
    Karolinska Univ Hopsital, Deprtment Thorac Surg, Stockholm, Sweden..
    Liv, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Branden, Eva
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Surgery in Elderly Patients ( > 70 Years or Older) with Non-Small Lung Cancer (NSCLC). Impact of Adjuvant Chemotherapy2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S674-S674Article in journal (Other academic)
  • 19.
    La Fleur, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Falk-Sörqvist, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Smeds, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Brandén, Eva
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Isaksson, Johan
    Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden.
    Brunnström, Hans
    Reg Labs Reg Skane, Pathol, Lund, Sweden.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Landelius, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Nilsson, Mats
    Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Moens, Lotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mutation Profiling by Targeted Next Generation Sequencing of an Unselected NSCLC Cohort2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S526-S527Article in journal (Other academic)
  • 20.
    La Fleur, Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Moens, Lotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Falk-Sörqvist, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Mattsson, Johanna S. M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Branden, Eva
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Brunnström, Hans
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, Lund, Sweden..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Isaksson, Johan
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Jirström, Karin
    Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, Lund, Sweden..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nilsson, Mats
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Mutation Profiling by Targeted Next-Generation Sequencing for Diagnostics and Patient Cohort Screening in FFPE NSCLC Samples2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S697-S697Article in journal (Other academic)
  • 21.
    Lantuejoul, Sylvie
    et al.
    Ctr Leon Berard Unicanc, Lyon, France.;Univ Grenoble Alpes, Grenoble, France..
    Sound-Tsao, Ming
    Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada..
    Cooper, Wendy A.
    Royal Prince Alfred Hosp, Camperdown, NSW, Australia..
    Girard, Nicolas
    Inst Curie, Paris, France.;Univ Claude Bernard, Lyon, France..
    Hirsch, Fred R.
    Tisch Canc Inst, Ctr Thorac Oncol, New York, NY USA.;Mt Sinai Hlth Syst, Ichan Sch Med, New York, NY USA..
    Roden, Anja C.
    Mayo Clin, Rochester, MN USA..
    Lopez-Rios, Fernando
    HM Hosp, Pathol Lab Dianas Terapeut, Madrid, Spain..
    Jain, Deepali
    All India Inst Med Sci, New Delhi, India..
    Chou, Teh-Ying
    Taipei Vet Gen Hosp, Taipei, Taiwan..
    Motoi, Noriko
    Natl Canc Ctr, Tokyo, Japan..
    Kerr, Keith M.
    Aberdeen Royal Infirm, Dept Pathol, Aberdeen, Scotland..
    Yatabe, Yasushi
    Brambilla, Elisabeth
    Univ Grenoble Alpes, Grenoble, France..
    Longshore, John
    Carolinas Pathol Grp, Charlotte, NC USA..
    Papotti, Mauro
    Univ Turin, Turin, Italy..
    Sholl, Lynette M.
    Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA..
    Thunnissen, Erik
    Vrije Univ Amsterdam, Dept Pathol, Med Ctr, Amsterdam, Netherlands..
    Rekhtman, Natasha
    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA..
    Borczuk, Alain
    Weill Cornell Med, New York, NY USA..
    Bubendorf, Lukas
    Univ Basel, Inst Pathol, Basel, Switzerland..
    Minami, Yuko
    Ibarakihigashi Natl Hosp, Tokai, Ibaraki, Japan..
    Beasley, Mary Beth
    Mt Sinai Hlth Syst, Ichan Sch Med, New York, NY USA..
    Botling, Johan
    Uppsala Univ Hosp, Uppsala, Sweden.
    Chen, Gang
    Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China..
    Chung, Jin-Haeng
    Seoul Natl Univ, Bundang Hosp, Seoul, South Korea..
    Dacic, Sanja
    Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA..
    Hwang, David
    Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada..
    Lin, Dongmei
    Peking Univ, Canc Hosp & Inst, Dept Pathol, Beijing, Peoples R China..
    Moreira, Andre
    NYU, Sch Med, New York, NY USA..
    Nicholson, Andrew G.
    Royal Brompton & Harefield NHS Fdn Trust, London, England.;Imperial Coll, Natl Heart & Lung Inst, London, England..
    Noguchi, Masayuki
    Univ Tsukuba, Tsukuba, Ibaraki, Japan..
    Pelosi, Giuseppe
    Univ Milan, Milan, Italy.;IRCCS MultiMed, Milan, Italy..
    Poleri, Claudia
    Off Pathol Consultants, Buenos Aires, DF, Argentina..
    Travis, William
    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA..
    Yoshida, Akihiko
    Natl Canc Ctr, Tokyo, Japan..
    Daigneault, Jillian B.
    Int Assoc Study Lung Canc, Aurora, CO USA..
    Wistuba, Ignacio I.
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Mino-Kenudson, Mari
    Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA..
    PD-L1 Testing for Lung Cancer in 2019: Perspective From the IASLC Pathology Committee2020In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 15, no 4, p. 499-519Article, review/survey (Refereed)
    Abstract [en]

    The recent development of immune checkpoint inhibitors (ICIs) has led to promising advances in the treatment of patients with NSCLC and SCLC with advanced or metastatic disease. Most ICIs target programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) axis with the aim of restoring antitumor immunity. Multiple clinical trials for ICIs have evaluated a predictive value of PD-L1 protein expression in tumor cells and tumor-infiltrating immune cells (ICs) by immunohistochemistry (IHC), for which different assays with specific IHC platforms were applied. Of those, some PD-L1 IHC assays have been validated for the prescription of the corresponding agent for first- or second-line treatment. However, not all laboratories are equipped with the dedicated platforms, and many laboratories have set up in-house or laboratory-developed tests that are more affordable than the generally expensive clinical trial-validated assays. Although PD-L1 IHC test is now deployed in most pathology laboratories, its appropriate implementation and interpretation are critical as a predictive biomarker and can be challenging owing to the multiple antibody clones and platforms or assays available and given the typically small size of samples provided. Because many articles have been published since the issue of the IASLC Atlas of PD-L1 Immunohistochemistry Testing in Lung Cancer, this review by the IASLC Pathology Committee provides updates on the indications of ICIs for lung cancer in 2019 and discusses important considerations on preanalytical, analytical, and postanalytical aspects of PD-L1 IHC testing, including specimen type, validation of assays, external quality assurance, and training.

  • 22. Lim, Eric
    et al.
    Goldstraw, Peter
    Nicholson, Andrew G.
    Travis, William D.
    Jett, James R.
    Ferolla, Piero
    Bomanji, Jamshed
    Rusch, Valerie W.
    Asamura, Hisao
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Baudin, Eric
    Caplin, Martyn
    Kwekkeboom, Dik
    Brambilla, Elisabeth
    Crowley, John
    Proceedings of the IASLC International Workshop on Advances in Pulmonary Neuroendocrine Tumors 20072008In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 3, no 10, p. 1194-1201Article in journal (Refereed)
    Abstract [en]

    The International Association for the Study of Lung Cancer, (IASLC) International Congress on Advances in Pulmonary Neuroendocrine Tumors was a two-day meeting held at the Royal Brompton Hospital in London, United Kingdom on the thirteenth and forteenth of December 2007. The meeting was led by 14 member international faculty-in the disciplines of pathology, surgery, medicine, oncology, endocrinology, nuclear medicine, diagnostic imaging, and biostatistics. The aims were twofold, as an educational meeting, and to develop the IASLC International Pulmonary Neuroendocrine Tumors Registry. The meeting highlighted the difference in presentation of the tumors, management options for early and advanced stage disease including the use of novel agents and approaches. The need, process, and approach to an International Registry of Pulmonary Neuroendocrine Tumors were emphasized. International collaboration to develop a retrospective registry, prospective data collection, virtual tissue bank, and collaborative clinical trials were universally agreed as the best way to advance our understanding and treatment of these rare tumors.

  • 23.
    Mattsson, Johanna S. M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Svensson, Maria A.
    Univ Orebro, Fac Med & Hlth, Dept Pathol, SE-70182 Orebro, Sweden..
    Hallström, Björn
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Koyi, Hirsh
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Branden, Eva
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden..
    Brunnström, Hans
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden..
    Edlund, Karolina
    Dortmund TU, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Grinberg, Marianna
    Dortmund TU, Dept Stat, Dortmund, Germany..
    Rahnenfuehrer, Joerg
    Dortmund TU, Dept Stat, Dortmund, Germany..
    Jirström, Karin
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden..
    Pontén, Fredrik
    Karlsson, Mats G.
    Univ Orebro, Fac Med & Hlth, Dept Pathol, SE-70182 Orebro, Sweden..
    Karlsson, Christina
    Univ Orebro, Fac Med & Hlth, Dept Pathol, SE-70182 Orebro, Sweden..
    Helenius, Gisela
    Univ Orebro, Fac Med & Hlth, Dept Pathol, SE-70182 Orebro, Sweden..
    Uhlen, Mathias
    KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    ALK Rearrangements in Non-Small Cell Lung Cancer: Comprehensive Integration of Genomic, Gene Expression and Protein Analysis2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S298-S298Article in journal (Other academic)
  • 24.
    Micke, Patrick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Göransson Kultima, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Scheibenflug, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Myrdal, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Berglund, Anders
    Andersson, Annsofie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lambe, Mats
    Nyberg, Fredrik
    Thomas, Andrew
    Isaksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Gene Copy Number Aberrations Are Associated with Survival in Histologic Subgroups of Non-small Cell Lung Cancer2011In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 6, no 11, p. 1833-1840Article in journal (Refereed)
    Abstract [en]

    Introduction:

    Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups.

    Methods:

    Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters.

    Results:

    Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively.

    Conclusion:

    Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.

  • 25.
    Micke, Patrick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Djureinovic, Dijana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Nodin, Björn
    Jirström, Karin
    Tran, Lena
    Jönsson, Per
    Planck, Maria
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Brunnström, Hans
    The Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs2016In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 11, no 6, p. 862-872Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Histopathological classification of lung cancer is of central importance in the diagnostic routine and guides therapy in the majority of patients. The 4(th) edition of the WHO classification was recently published and includes changes to the diagnostic procedure of non-small cell carcinomas (NSCC) with more emphasis on immunohistochemical (IHC) staining.

    METHODS: 656 unselective cases of resected pulmonary NSCC were diagnosed according to the 2004 WHO classification. After IHC staining with cytokeratin 5, p40, p63, thyroid transcription factor 1 (clones 8G7G3/1 and SPT24) and napsin A the diagnoses were revised in accordance with the new 4(th) edition of the WHO classification.

    RESULTS: Reclassification led to a new histological annotation in 36 (5%) of the 656 cases. Most notable was the decrease of cases previously classified as large cell carcinomas (56 vs. 12 cases). This was partially due to the exclusion of 21 neuroendocrine tumors from this group, while 20 cases were ascribed to the group of adenocarcinoma based on IHC markers. Only 7 cases of adenocarcinoma or squamous cell carcinoma were reclassified after the addition of IHC staining. There was a substantial overlap in staining properties between different markers of squamous and adenocarcinomatous differentiation, respectively, but in 17-31 cases (3-5%) the diagnosis depended on the choice of markers.

    CONCLUSIONS: The 4(th) edition of the WHO classification of lung tumours leads to changes of histological type in 5% of resected NSCC cases. The incorporation of IHC staining in NSCC diagnostics demands awareness that the choice of ancillary stains has an effect on diagnosis.

  • 26.
    Miyashita, Naoya
    et al.
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
    Horie, Masafumi
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan;Univ Southern Calif, Hastings Ctr Pulm Res, Div Pulm Crit Care & Sleep Med, Dept Med,Keck Sch Med, Los Angeles, CA USA;RIKEN Ctr Life Sci Technol, Div Genom Technol, Yokohama, Kanagawa, Japan.
    Suzuki, Hiroshi I.
    MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Yoshihara, Masahito
    RIKEN Ctr Life Sci Technol, Div Genom Technol, Yokohama, Kanagawa, Japan.
    Djureinovic, Dijana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Persson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Brunnstrom, Hans
    Lund Univ, Lab Med Reg Skane, Dept Clin Sci Lund, Pathol, Lund, Sweden.
    Lindskog, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Elfving, Hedvig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Saito, Akira
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan;Univ Tokyo, Div Hlth Serv Promot, Tokyo, Japan.
    Nagase, Takahide
    Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
    An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 11, p. 1676-1691Article in journal (Refereed)
    Abstract [en]

    Introduction: A subgroup of lung adenocarcinoma shows neuroendocrine differentiation and expression of achaete-scute family bHLH transcription factor 1 (ASCL1), common to high-grade neuroendocrine tumors, small-cell lung cancer and large cell neuroendocrine carcinoma. Methods: The aim of this study was to characterize clinical and molecular features of ASCL1-positive lung adenocarcinoma by using recent transcriptome profiling in multiple patient cohorts and genome-wide epigenetic profiling including data from The Cancer Genome Atlas. Results: The ASCL1-positive subtype of lung adenocarcinoma developed preferentially in current or former smokers and usually did not harbor EGFR mutations. In transcriptome profiling, this subtype overlapped with the recently proposed proximal-proliferative molecular subtype. Gene expression profiling of ASCL1-positive cases suggested generally poor immune cell infiltration and none of the tumors were positive for programmed cell death ligand 1 protein expression. Genome-wide methylation analysis showed global DNA hypomethylation in ASCL1-positive cases. ASCL1 was associated with super-enhancers in ASCL1-positive lung adenocarcinoma cells, and ASCL1 silencing suppressed other super-enhancer-associated genes, suggesting thatASCL1 acts as a master transcriptional regulator. This was further reinforced by the essential roles of ASCL1 in cell proliferation, survival, and cell cycle control. Conclusions: These results suggest that ASCL1 defines a subgroup of lung adenocarcinoma with distinct molecular features by driving super-enhancer-mediated transcriptional programs.

  • 27.
    Nicholson, Andrew G.
    et al.
    Royal Brompton & Harefield Natl Hlth Serv Fdn Tru, London, England.;Imperial Coll, Natl Heart & Lung Inst, London, England..
    Torkko, Kathleen
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA..
    Viola, Patrizia
    Royal Brompton & Harefield Natl Hlth Serv Fdn Tru, London, England.;Imperial Coll, Natl Heart & Lung Inst, London, England..
    Duhig, Edwina
    Sullivan Nicolaides Pathol, Taringa, Qld, Australia..
    Geisinger, Kim
    Univ Mississippi, Med Ctr, Jackson, MS 39216 USA..
    Borczuk, Alain C.
    Weill Cornell Med, New York, NY USA..
    Hiroshima, Kenzo
    Tokyo Womens Med Univ, Yachiyo, Japan..
    Tsao, Ming S.
    Princess Margaret Canc Ctr, Toronto, ON, Canada.;Univ Toronto, Toronto, ON, Canada..
    Warth, Arne
    Heidelberg Univ Hosp, Heidelberg, Germany..
    Lantuejoul, Sylvie
    Canc Inst Leon Berard, Lyon, France..
    Russell, Prudence A.
    St Vincents Pathol, Fitzroy, Vic, Australia..
    Thunnissen, Erik
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Marchevsky, Alberto
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Mino-Kenudson, Mari
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Beasley, Mary Beth
    Mt Sinai Med Ctr, New York, NY 10029 USA..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dacic, Sanja
    Univ Pittsburgh, Pittsburgh, PA USA..
    Yatabe, Yasushi
    Aichi Canc Ctr, Nagoya, Aichi, Japan..
    Noguchi, Masayuki
    Univ Tsukuba, Tsukuba, Ibaraki, Japan..
    Travis, William D.
    Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA..
    Kerr, Keith
    Aberdeen Royal Infirm, Aberdeen, Scotland..
    Hirsch, Fred R.
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA..
    Chirieac, Lucian R.
    Harvard Med Sch, Boston, MA USA..
    Wistuba, Ignacio I.
    MD Anderson, Houston, TX USA..
    Moreira, Andre
    NYU, Langone Med Ctr, New York, NY USA..
    Chung, Jin-Haeng
    Seoul Natl Univ, Bundang Hosp, Seoul, South Korea..
    Chou, Teh Ying
    Taipei Vet Gen Hosp, Taipei, Taiwan..
    Bubendorf, Lukas
    Univ Hosp Basel, Basel, Switzerland..
    Chen, Gang
    Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China..
    Pelosi, Giuseppe
    Univ Milan, Dept Oncol & Hematooncol, Milan, Italy..
    Poleri, Claudia
    Detterbeck, Frank C.
    Yale Univ, Dept Thorac Surg, New Haven, CT USA..
    Franklin, Wilbur A.
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA..
    Interobserver Variation among Pathologists and Refinement of Criteria in Distinguishing Separate Primary Tumors from Intrapulmonary Metastases in Lung2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 2, p. 205-217Article in journal (Refereed)
    Abstract [en]

    Multiple tumor nodules are seen with increasing frequency in clinical practice. On the basis of the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment to distinguish second primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs), looking for the most distinctive histologic features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients and recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM, or a combination thereof. Cohen kappa statistics of 0.60 on overall assessment of SPLC or IPM indicated a good agreement. Likewise, there was good agreement (kappa score 0.64, p < 0.0001) between WHO histologic pattern in individual cases and SPLC or IPM status, but the proportions diversified for histologic pattern and SPLC or IPM status (McNemar test, p < 0.0001). The strongest associations for distinguishing between SPLC and IPM were observed for nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intraalveolar clusters, and necrosis. Conversely, the associations for lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization, and emperipolesis did not reach significance with tumor extent. Comprehensive histologic assessment is recommended for distinguishing SPLC from IPM with good reproducibility among lung pathologists. In addition to main histologic type and predominant patterns of histologic subtypes, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate strongly correlate with pathologic staging status.

  • 28.
    Nicholson, Andrew
    et al.
    Royal Brompton & Harefield NHS Fdn, Pathol, London, England.;Natl Heart & Lung Inst, London, England..
    Viola, Patrizia
    Royal Brompton & Harefield NHS Fdn, Pathol, London, England.;Natl Heart & Lung Inst, London, England..
    Torkko, Kathleen
    Univ Colorado, Pathol, Anschutz Med Campus, Aurora, CO USA..
    Duhig, Edwina
    Sullivan Nicolaides Pathol, Taringa, Qld, Australia..
    Geisinger, Kim
    Piedmont Pathol Associates Inc, Hickory Corners, MI USA..
    Borczuk, Alain
    Weill Cornell Med, New York, NY USA..
    Hiroshima, Kenzo
    Tokyo Womens Med Univ, Yachiyo, Pathol, Tokyo, Japan..
    Tsao, Ming
    Princess Margaret Canc Ctr, Dept Pathol, Toronto, ON, Canada.;Univ Toronto, Toronto, ON, Canada..
    Warth, Arne
    Heidelberg Univ Hosp, Inst Pathol, Heidelberg, Germany..
    Lantuejoul, Sylvie
    Canc Inst Leon Berard, Biopathol, Lyon, France..
    Russell, Prudence
    St Vincents Pathol, Fitzroy, Vic, Australia..
    Thunnissen, Erik
    Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands..
    Marchevsky, Alberto
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Mino-Kenudson, Mari
    Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA..
    Beasley, Mary Beth
    Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA..
    Boding, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Dacic, Sanja
    Univ Pittsburgh, Pathol, Pittsburgh, PA USA..
    Yatabe, Yasushi
    Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Nagoya, Aichi, Japan..
    Noguchi, Masayuki
    Univ Tsukuba, Fac Med, Dept Pathol, Tsuruga, Fukui, Japan..
    Travis, William
    Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA..
    Kerr, Keith
    Aberdeen Royal Infirm, Pathol, Aberdeen, Scotland..
    Hirsch, Fred R.
    Univ Colorado, Div Med Oncol, Anschutz Med Campus, Aurora, CO USA..
    Chirieac, Lucian
    Harvard Med Sch, Dept Pathol, Boston, MA USA..
    Wistuba, Ignacio
    MD Anderson, Translat Mol Pathol, Houston, TX USA..
    Moreira, Andre
    NYU Langone Med Ctr, Pathol, New York, NY USA..
    Chung, Jin-Haeng
    Seoul Natl Univ, Bundang Hosp, Pathol, Seoul, South Korea..
    Chou, Teh Ying
    Taipei Vet Gen Hosp, Dept Pathol, Taipei, Taiwan..
    Bubendorf, Lukas
    Taipei Vet Gen Hosp, Lab Med, Taipei, Taiwan.;Univ Basel Hosp, Inst Pathol, Basel, Switzerland..
    Chen, Gang
    Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai, Peoples R China..
    Pelosi, Giuseppe
    Univ Milan, Dept Oncol & Hematooncol, Milan, Italy..
    Poleri, Claudia
    Pathology, Buenos Aires, Argentina..
    Franklin, Wilbur
    Univ Colorado, Pathol, Anschutz Med Campus, Aurora, CO USA..
    Reproducibility of Comprehensive Histologic Assessment and Refining Histologic Criteria in P Staging of Multiple Tumor Nodules2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S1131-S1132Article in journal (Other academic)
  • 29. Nisman, Benjamin
    et al.
    Nechushtan, Hovav
    Biran, Haim
    Gantz-Sorotsky, Hadas
    Peled, Nir
    Gronowitz, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Peretz, Tamar
    Serum Thymidine Kinase 1 Activity in the Prognosis and Monitoring of Chemotherapy in Lung Cancer Patients: A Brief Report2014In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 9, no 10, p. 1568-1572Article in journal (Refereed)
    Abstract [en]

    Introduction: Thymidine kinase 1 (TK1) is a metabolic enzyme involved in DNA synthesis. Most standard treatment protocols for lung cancer (LC) include cytotoxic agents, which are potential modulators of TK1. We aimed to assess the prognostic significance of serum TK1 activity and its role in monitoring chemotherapy in LC patients. Methods: TK1 activity was measured using the DiviTum (Biovica) assay in sera from 233 patients with non-small-cell lung cancer (NSCLC), 91 with small-cell lung cancer (SCLC), and 90 with benign lung disease. Results: TK1 activity was significantly associated with age, performance status, and stage in NSCLC and with stage and weight loss in SCLC. In multivariate analysis, pretreatment TK1 activity, adjusted for performance status, stage, and weight loss, independently affected survival in NSCLC (relative risk = 1.45, p = 0.031) and SCLC (relative risk = 2.49, p = 0.001). In NSCLC patients, adjusted elevated TK1 activity (>100 Du/L) at pretreatment was a significant predictor of treatment failure (odds ratio = 2.55, p = 0.01). A small (less than twofold) increase in TK1 activity after the first and second cycle of chemotherapy was significantly associated with treatment failure and poor overall survival. Conclusions: Elevated pretreatment serum TK1 activity was an independent, adverse prognostic factor, based on survival, in the two main histological types of LC. A small (less than twofold) increase in TK1 activity after the first and second cycle of chemotherapy was associated with treatment failure and poor overall survival.

  • 30.
    Salanova, R.
    et al.
    Hosp Gastroenterol Dr Carlos Bonorino Udaonda, Buenos Aires, DF, Argentina.
    Dietel, M.
    Charite Univ Med Berlin, Inst Pathol, Berlin, Germany.
    Savelov, N.
    Moscow Oncol Hosp, Moscow, Russia.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Bigras, G.
    Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada.
    Hida, T.
    Aichi Canc Ctr, Dept Thorac Oncol, Nagoya, Aichi, Japan.
    Piperdi, B.
    Merck & Co Inc, Kenilworth, NJ USA.
    Burke, T.
    Merck & Co Inc, Kenilworth, NJ USA.
    Khambata-Ford, S.
    Merck & Co Inc, Kenilworth, NJ USA.
    Deitz, A.
    Merck & Co Inc, Kenilworth, NJ USA.
    Real-World Prevalence of PD-L1 Expression in Advanced NoneSmall-Cell Lung Cancer: The Global, Multicenter EXPRESS Study2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 9, p. S155-S156Article in journal (Other academic)
  • 31.
    Salomonsson, A.
    et al.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden.
    Patthey, A.
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Reutersward, C.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden.
    Jonsson, M.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Brunnstrom, H.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden.
    Hussein, A.
    Sahlgrens Univ Hosp, Dept Clin Pathol & Genet, Gothenburg, Sweden.
    Monsef, N.
    Linkoping Univ, Dept Clin & Expt Med, Pathol, Linkoping, Sweden.
    Ortiz-Villalon, C.
    Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden.
    Bergman, B.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    De Petris, L.
    Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Viltstrom, A.
    Linkoping Univ Hosp, Dept Resp Med, Linkoping, Sweden.
    Wagenius, G.
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
    Behndig, A.
    Umea Univ, Div Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Johansson, M.
    Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Koyi, Hirsh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Staaf, J.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden.
    Planck, M.
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden.
    A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 10, p. S431-S432Article in journal (Other academic)
  • 32.
    Sandelin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Berglund, Anders
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    EGFR-Mutations and Resulting Treatment in a Nsclc Population-Based Cohort in Central Sweden2013In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 8, no S2, p. S904-S905Article in journal (Other academic)
  • 33.
    Thunnissen, Erik
    et al.
    Vrije Univ Amsterdam Med Ctr, Dept Pathol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands..
    Borczuk, Alain C.
    Weill Cornell Med, Dept Pathol, New York, NY USA..
    Flieder, Douglas B.
    Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA..
    Witte, Birgit
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands..
    Beasley, Mary Beth
    Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA..
    Chung, Jin-Haeng
    Seoul Natl Univ, Bundang Hosp, Coll Med, Dept Pathol, Seoul 151, South Korea..
    Dacic, Sanja
    Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA..
    Lantuejoul, Sylvie
    Ctr Leon Berard UNICANCER, Dept Biopathol, Lyon, France..
    Russell, Prudence A.
    St Vincent Pathol, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia..
    den Bakker, Michael
    Maasstad Ziekenhuis, Dept Pathol, Rotterdam, Netherlands..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Brambilla, Elisabeth
    CHU Albert Michallon, Inst Biol, Dept Anat & Cytol Pathol, Grenoble, France..
    de Cuba, Erienne
    Vrije Univ Amsterdam Med Ctr, Dept Pathol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands..
    Geisinger, Kim R.
    Univ Mississippi, Med Ctr, Dept Pathol, Jackson, MS 39216 USA..
    Hiroshima, Kenzo
    Tokyo Womens Med Univ, Yachiyo Med Ctr, Dept Pathol, Yachiyo, Japan..
    Marchevsky, Alberto M.
    Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA..
    Minami, Yuko
    Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Tsukuba, Ibaraki, Japan..
    Moreira, Andre
    NYU, Ctr Biospecimen Res & Dev, Pulm Pathol, New York, NY USA..
    Nicholson, Andrew G.
    Royal Brompton & Harefield Hosp Natl Hlth Serv Fd, Dept Histopathol, London, England.;Imperial Coll, Natl Heart & Lung Inst, London, England..
    Yoshida, Akihiko
    Natl Canc Ctr, Dept Pathol & Clin Labs, Tokyo, Japan..
    Tsao, Ming-Sound
    Princess Margaret Hosp, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada.;Univ Toronto, Toronto, ON, Canada..
    Warth, Arne
    Heidelberg Univ, Inst Pathol, Heidelberg, Germany..
    Duhig, Edwina
    John Flynn Hosp, Sullivan Nicolaides Pathol, Tugun, Qld, Australia..
    Chen, Gang
    Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai, Peoples R China..
    Matsuno, Yoshihiro
    Hokkaido Univ Hosp, Dept Surg Pathol, Sapporo, Hokkaido, Japan..
    Travis, William D.
    Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA..
    Butnor, Kelly
    Univ Vermont, Dept Pathol, Burlington, VT 05405 USA..
    Cooper, Wendy
    Royal Prince Alfred Hosp, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia..
    Mino-Kenudson, Mari
    Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Motoi, Noriko
    Natl Canc Ctr, Dept Pathol & Clin Labs, Tokyo, Japan..
    Poleri, Claudia
    Lab Patol Torac, Buenos Aires, DF, Argentina..
    Pelosi, Giuseppe
    Univ Milan, Dept Oncol & Hematol Oncol, Milan, Italy..
    Kerr, Keith
    Aberdeen Royal Infirm, Dept Pathol, Aberdeen, Scotland..
    Aisner, Seena C.
    Rutgers State Univ, Rutgers New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ USA..
    Ishikawa, Yuichi
    Japan Fdn Canc Res, Inst Canc, Div Pathol, Tokyo, Japan..
    Buettner, Reinhard H.
    Cologne Inst Pathol, Cologne, Germany..
    Keino, Naoto
    Univ Tsukuba, Tsukuba Clin Res & Dev Org, Tsukuba, Ibaraki, Japan..
    Yatabe, Yasushi
    Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Nagoya, Aichi, Japan..
    Noguchi, Masayuki
    Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Tsukuba, Ibaraki, Japan..
    The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 2, p. 334-346Article in journal (Refereed)
    Abstract [en]

    Introduction: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise K scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC.

    Methods: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3).

    Results: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, K scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64.

    Conclusions: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided. (C) 2017 International Association for the Study of Lung Cancer.

  • 34.
    Thunnissen, Erik
    et al.
    Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands.
    Borczuk, Alain
    Weill Cornell Med, New York, NY USA.
    Flieder, Douglas
    Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
    Witte, Birgit
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
    Beasley, Mary
    Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA.
    Chung, Jin-Haeng
    Seoul Natl Univ, Coll Med, Bundang Hosp, Seoul, South Korea.
    Dacic, Sanja
    Univ Pittsburgh, Pathol, Pittsburgh, PA USA.
    Lantuejoul, Sylvie
    Canc Inst Leon Berard, Biopathol, Lyon, France.
    Russell, Prudence
    St Vincents Pathol, Fitzroy, Vic, Australia.
    Den Bakker, Michael
    Maasstad Ziekenhuis, Rotterdam, Netherlands.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Brambilla, Elisabeth
    Chu Grenoble, Pathol, Grenoble, France;INSERM, Grenoble, France.
    De Cuba, Erienne
    Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands.
    Geisinger, Kim
    Piedmont Pathol Associates Inc, Hickory, NC USA.
    Hiroshima, Kenzo
    Tokyo Womens Med Univ, Pathol, Yachiyo, Japan.
    Marchevsky, Alberto
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
    Minami, Yuko
    Ibarakihigashi Natl Hosp, Natl Hosp Org, Pathol, Tokai, Ibaraki, Japan.
    Moreira, Andre
    Mem Sloan Kettering Canc Ctr, Pathol, 1275 York Ave, New York, NY 10021 USA.
    Nicholson, Andrew
    Royal Brompton & Harefield NHS Fdn Trust, Pathol, London, England;Natl Heart & Lung Inst, London, England.
    Yoshida, Akihiko
    Natl Canc Ctr, Dept Pathol, Tokyo, Japan.
    Tsao, Ming
    Princess Margaret Canc Ctr, Dept Pathol, Toronto, ON, Canada;Univ Toronto, Toronto, ON, Canada.
    Warth, Arne
    Heidelberg Univ Hosp, Heidelberg, Germany.
    Duhig, Edwina
    Sullivan Nicolaides Pathol, Taringa, Qld, Australia.
    Chen, Gang
    Fudang Univ, Zhongshan Hosp, Dept Pathol, Shanghai, Peoples R China.
    Matsuno, Yoshihiro
    Hokkaido Univ Hosp, Dept Surg Pathol, Sapporo, Hokkaido, Japan.
    Travis, William
    Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
    Butnor, Kelly
    Univ Vermont, Dept Pathol, Med Ctr, Burlington, VT 05405 USA.
    Cooper, Wendy
    Royal Prince Alfred Hosp, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia.
    Mino-Kenudson, Mari
    Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA.
    Motoi, Noriko
    Natl Canc Ctr, Dept Pathol, Tokyo, Japan.
    Polari, Claudia
    Lab Patol Torac, Buenos Aires, DF, Argentina.
    Pelosi, Giuseppe
    Univ Milan, Dept Oncol & Hematooncol, Milan, Italy.
    Kerr, Keith
    Aberdeen Royal Infirm, Pathol, Aberdeen, Scotland.
    Ishikawa, Yuichi
    Jfcr, Canc Inst, Tokyo, Japan.
    Buettner, Reinhard
    Cologne Inst Pathol, Cologne, Germany.
    Keino, Naoto
    Inst Basic Med Sci, Dept Biostat, Tsukuba, Ibaraki, Japan.
    Yatabe, Yasushi
    Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Nagoya, Aichi, Japan.
    Noguchi, Masayuki
    Univ Tsukuba, Fac Med, Dept Pathol, Tsukuba, Ibaraki, Japan.
    The Use of Immunohistochemistry Improves the Diagnosis of SCLC. An International Reproducibility Study in a Demanding Set of Cases2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 1, p. S1454-S1455Article in journal (Other academic)
  • 35.
    Tsao, Ming Sound
    et al.
    Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Pathol, Toronto, ON, Canada.
    Kerr, Keith M.
    Aberdeen Univ Med Sch, Aberdeen Royal Infirm, Dept Pathol, Aberdeen, Scotland.
    Kockx, Mark
    HistoGeneX, Antwerp, Belgium.
    Beasley, Mary-Beth
    Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA.
    Borczuk, Alain C.
    Weill Cornell Med, Dept Pathol, New York, NY USA.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Bubendorf, Lukas
    Univ Hosp Basel, Pathol, Inst Pathol, Basel, Switzerland.
    Chirieac, Lucian
    Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Chen, Gang i
    Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai 200433, Peoples R China.
    Chou, Teh-Ying
    Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Div Mol Pathol, Taipei, Taiwan.
    Chung, Jin-Haeng
    Seoul Natl Univ, Bundang Hosp, Dept Pathol, Seongnam City, Gyeonggi Do, South Korea;Seoul Natl Univ, Bundang Hosp, Resp Ctr, Seongnam City, Gyeonggi Do, South Korea.
    Dacic, Sanja
    Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
    Lantuejoul, Sylvie
    Ctr Leon Berard, Dept Biopathol, Lyon, France.
    Mino-Kenudson, Mari
    Harvard Med Sch, Boston, MA USA;Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
    Moreira, Andre L.
    NYU Langone Hlth, Dept Pathol, New York, NY USA.
    Nicholson, Andrew G.
    Royal Brompton & Harefield Natl Hlth Serv Fdn Tru, Dept Histopathol, London, England;Imperial Coll, Natl Heart & Lung Inst, London, England.
    Noguchi, Masayuki
    Univ Tsukuba, Fac Med, Dept Pathol, Tsukuba, Ibaraki, Japan.
    Pelosi, Giuseppe
    Univ Milan, Dept Oncol & Hematooncol, Milan, Italy;MultiMedica, IRCCS Grp, Milan, Italy.
    Poleri, Claudia s
    Off Pathol Consultants, Buenos Aires, DF, Argentina.
    Russell, Prudence A.
    St Vincents Pathol, Fitzroy, Vic, Australia.
    Sauter, Jennifer
    Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA.
    Thunnissen, Erik
    Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands.
    Wistuba, Ignacio
    MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX USA.
    Yu, Hui
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA.
    Wynes, Murry W.
    Int Assoc Study Lung Canc, Aurora, CO USA.
    Pintilie, Melania
    Univ Hlth Network, Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada.
    Yatabe, Yasushi
    Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Nagoya, Aichi, Japan.
    Hirsch, Fred R.
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA;Int Assoc Study Lung Canc, Aurora, CO USA.
    PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project2018In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 13, no 9, p. 1302-1311Article in journal (Refereed)
    Abstract [en]

    Objectives: The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples.

    Methods: BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials.

    Results: The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86–0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18–0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78–0.85).

    Conclusion: BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.

  • 36.
    Yatabe, Yasushi
    et al.
    Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Nagoya, Aichi, Japan.
    Dacic, Sanja
    Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
    Borczuk, Alain C.
    Weill Cornell Med, Dept Pathol, New York, NY USA.
    Warth, Arne
    Inst Pathol Cytopathol & Mol Pathol MVZ UEGP Gies, Wetzlar, Limburg, Germany.
    Russell, Prudence A.
    St Vincents Hosp, Dept Anat Pathol, Fitzroy, Vic, Australia;Univ Melbourne, Fitzroy, Vic, Australia.
    Lantuejoul, Sylvie
    Grenoble Alpes Univ, Dept Biopathol, Ctr Leon Berard, Lyon, France.
    Beasley, Mary Beth
    Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA.
    Thunnissen, Erik
    Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands.
    Pelosi, Giuseppe
    Univ Milan, Dept Oncol & Hematooncol, Milan, Italy;IRCCS MultiMed, Milan, Italy.
    Rekhtman, Natasha
    Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
    Bubendorf, Lukas
    Univ Hosp Basel, Inst Pathol, Basel, Switzerland.
    Mino-Kenudson, Mari
    Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Yoshida, Akihiko
    Natl Canc Ctr, Dept Pathol & Clin Labs, Tokyo, Japan.
    Geisinger, Kim R.
    Univ Mississippi, Med Ctr, Dept Pathol, Jackson, MS 39216 USA.
    Noguchi, Masayuki
    Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Tsukuba, Ibaraki, Japan.
    Chirieac, Lucian R.
    Harvard Med Sch, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chung, Jin-Haeng
    Seoul Natl Univ, Bundang Hosp, Dept Pathol, Seongnam City, Gyeonggi Do, South Korea;Seoul Natl Univ, Bundang Hosp, Resp Ctr, Seongnam City, Gyeonggi Do, South Korea.
    Chou, Teh-Ying
    Taipei Vet Gen Hosp, Div Mol Pathol, Dept Pathol & Lab Med, Taipei, Taiwan.
    Chen, Gang
    Fudan Univ, Dept Pathol, Zhongshan Hosp, Shanghai, Peoples R China.
    Poleri, Claudia
    Off Pathol Consultants, Buenos Aires, DF, Argentina.
    Lopez-Rios, Fernando
    Hosp Univ HM Sanchinarro, Lab Dianas Terapeut, Madrid, Spain.
    Papotti, Mauro
    Univ Turin, Dept Oncol, Turin, Italy.
    Sholl, Lynette M.
    Harvard Med Sch, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
    Roden, Anja C.
    Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
    Travis, William D.
    Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
    Hirsch, Fred R.
    Univ Colorado, Anschutz Med Campus, Aurora, CO USA.
    Kerr, Keith M.
    Univ Aberdeen, Sch Med, Dept Pathol, Aberdeen Royal Infirm, Aberdeen, Scotland.
    Tsao, Ming-Sound
    Univ Toronto, Dept Pathol, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
    Nicholson, Andrew G.
    Imperial Coll, Dept Histopathol, Royal Brompton & Harefield Natl Hlth Serv Fdn Tru, London, England;Imperial Coll, Natl Heart & Lung Inst, London, England.
    Wistuba, Ignacio
    Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.
    Moreira, Andre L.
    New York Univ Langone Hlth, Dept Pathol, New York, NY USA.
    Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer2019In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 14, no 3, p. 377-407Article in journal (Refereed)
    Abstract [en]

    Since the 2015 WHO classification was introduced into clinical practice, immunohistochemistry (IHC) has figured prominently in lung cancer diagnosis. In addition to distinction of small cell versus non-small cell carcinoma, patients' treatment of choice is directly linked to histologic subtypes of non-small cell carcinoma, which pertains to IHC results, particularly for poorly differentiated tumors. The use of IHC has improved diagnostic accuracy in the classification of lung carcinoma, but the interpretation of IHC results remains challenging in some instances. Also, pathologists must be aware of many interpretation pitfalls, and the use of IHC should be efficient to spare the tissue for molecular testing. The International Association for the Study of Lung Cancer Pathology Committee received questions on practical application and interpretation of IHC in lung cancer diagnosis. After discussions in several International Association for the Study of Lung Cancer Pathology Committee meetings, the issues and caveats were summarized in terms of 11 key questions covering common and important diagnostic situations in a daily clinical practice with some relevant challenging queries. The questions cover topics such as the best IHC markers for distinguishing NSCLC subtypes, differences in thyroid transcription factor 1 clones, and the utility of IHC in diagnosing uncommon subtypes of lung cancer and distinguishing primary from metastatic tumors. This article provides answers and explanations for the key questions about the use of IHC in diagnosis of lung carcinoma, representing viewpoints of experts in thoracic pathology that should assist the community in the appropriate use of IHC in diagnostic pathology.

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