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  • 1.
    Aasebö, Kristine Ö.
    et al.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mezheyeuski, Artur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Eide, Geir Egil
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Ctr Clin Res, Bergen, Norway.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sorbye, Halfdan
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients2019In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 7, p. 3623-3635Article in journal (Refereed)
    Abstract [en]

    Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.

    Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.

    Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).

    Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).

  • 2.
    Abdulla, Maysaa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Prognostic signficance of tumor cell markers in diffuse large B-cell lymphoma with special emphasis on lymphoma localization2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of high-grade B-cell lymphoma with different clinical, morphological, immunophenotypical, and molecular features. DLBCL is curable in 60-70% of patients when treated with standard immunochemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone).

    The main aim of this thesis is to identify prognostic factors in DLBCL by studying tumor markers (paper I and II), site of disease (paper III) and tumor microenvironment markers in primary DLBCL of the CNS (PCNSL) (paper IV) in order to better identify different risk groups of DLBCL patients.

    In papers I-III, we studied DLBCL patients treated homogeneously with R-CHOP. The negative prognostic impact of double protein expression of MYC and BCL2 so called “double-expressor lymphoma” (DEL) was a common finding in the three papers. In paper I, we detected DEL in 27% of patients, distributed with no significant difference between the germinal center derived B-cell subgroup (GCB) in 52% of cases and the non-GCB subgroup in 37% of cases. There was no significant difference in survival between GCB and non-GCB patients. The diagnosis in most of the patients with DEL was made on core needle biopsy in this paper. This finding was more thoroughly investigated in paper III with attention paid to the site of biopsy. In paper II, we evaluated the concordance of cell of origin (COO) assignment between gene expression profile (GEP) and immunohistochemistry (IHC) to identify the best predictor of survival in a DLBCL cohort including patients from Sweden and Denmark. The overall concordance between the two methods was 83%. We found that ABC/non-GCB subtype identified by both GEP and IHC is associated with the worst outcome. This finding indicates the importance of precise risk stratification in the era of precision medicine. DEL was more common in ABC patients categorized by GEP. In paper III, we identified abdominal lymph node involvement by radiological examination in 63% of DLBCL patients with an inferior survival, adverse clinical characteristics and significantly more frequent DEL. These findings may indicate a distinct biological behavior in patients with abdominal nodal disease. In paper IV, we demonstrated a significant association between IDO1 and PD-L1 in PCNSL patients. This finding indicates the crucial immunosuppressive role of these two molecules. In addition, in PCNSL low frequencies of MYC and BCL2 translocations and high frequency of BCL6 translocation was observed and DEL was detected in 49% of cases. Contrary to our results in systemic DLBCL in papers I-III, there was no significant prognostic impact of DEL in PCNSL.

    List of papers
    1. A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients
    Open this publication in new window or tab >>A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients
    Show others...
    2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 9-10, p. 1126-1131Article in journal (Refereed) Published
    Abstract [en]

    Aim: To determine the prognostic significance of co-expression of MYC, BCL-2 and BCL-6 proteins in combination with other biomarkers and clinical characteristics within a population-based cohort of diffuse large B-cell lymphoma (DLBCL) patients uniformly treated with R-CHOP.

    Patients and methods: The immunohistochemical (IHC) expression of CD10, BCL-2, BCL-6, MUM1, MYC, CD5, CD30, Ki-67 and p53 was evaluated in a retrospective, population-based study comprising 188 DLBCL patients treated with R-CHOP and diagnosed in Sweden between 2002 and 2012.

    Results: Patients had a median age at diagnosis of 64 years (26-85 years) with a male:female ratio of 1.4:1. Approximately half (52%) of the patients presented with an International Prognostic Index (IPI) age adjusted (IPIaa)2. Median follow-up time was 51 months (range 0.4-158) and the five-year lymphoma-specific survival (LSS) was 76%, five-year overall survival (OS) was 65% and five-year progression-free survival (PFS) was 61%. A high Ki-67 value was found in 59% of patients, while p53 overexpression was detected in 12% of patients and MYC, BCL-2 and BCL-6 expression were detected in 42%, 55% and 74% of patients, respectively. IPIaa2 (p=0.002), Ki-6770% (p=0.04) and p53 overexpression50% (p=0.02) were associated with inferior LSS and OS. Co-expression of both MYC (>40%) and BCL-2 (>70%) proteins was detected in 27% of patients and correlated with a significantly inferior LSS (p=0.0002), OS (p=0.009) and PFS (p=0.03). In addition, triple expression of MYC, BCL-2 and BCL-6, also correlated with a significantly inferior LSS (p=0.02).

    Conclusion: Concurrent expression of MYC and BCL-2 proteins, as detected by IHC, was strongly associated with an inferior survival in DLBCL patients treated with R-CHOP. Other markers affecting survival were triple expression of MYC, BCL-2 and BCL-6, IPIaa, high Ki-67 and p53 overexpression.

    National Category
    Cancer and Oncology Clinical Laboratory Medicine
    Research subject
    Pathology
    Identifiers
    urn:nbn:se:uu:diva-308051 (URN)10.1080/0284186X.2016.1189093 (DOI)000385554200010 ()
    Funder
    Swedish Cancer Society
    Available from: 2016-11-24 Created: 2016-11-23 Last updated: 2020-01-31Bibliographically approved
    2. Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma
    Open this publication in new window or tab >>Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma
    Show others...
    2019 (English)In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

    National Category
    Hematology Clinical Laboratory Medicine
    Research subject
    Pathology
    Identifiers
    urn:nbn:se:uu:diva-397669 (URN)10.1002/ajh.25666 (DOI)000495085000001 ()31659781 (PubMedID)
    Funder
    Swedish Cancer SocietySwedish Research Council
    Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2020-01-31Bibliographically approved
    3. Prognostic impact of abdominal lymph node involvement in diffuse large B-cell lymphoma
    Open this publication in new window or tab >>Prognostic impact of abdominal lymph node involvement in diffuse large B-cell lymphoma
    Show others...
    2020 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 3, p. 207-213Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: The prognostic value of site of nodal involvement in diffuse large B-cell lymphomas (DLBCL) is mainly unknown. We aimed to determine the prognostic significance of nodal abdominal involvement in relation to tumour cell markers and clinical characteristics of 249 DLBCL patients in a retrospective single-centre study.

    METHODS: Contrast-enhanced computed tomography (CT) of the abdomen and thorax revealed pathologically enlarged abdominal lymph nodes in 156 patients, while in 93 patients there were no pathologically enlarged lymph nodes in the abdomen. In 81 cases, the diagnosis of DLBCL was verified by histopathological biopsy obtained from abdominal lymph node.

    RESULTS: Patients with abdominal nodal disease had inferior lymphoma-specific survival (P = .04) and presented with higher age-adjusted IPI (P < .001), lactate dehydrogenase (P < .001) and more often advanced stage (P < .001), bulky disease (P < .001), B symptoms (P < .001), and double expression of MYC and BCL2 (P = .02) compared to patients without nodal abdominal involvement, but less often extranodal involvement (P < .02). The worst outcome was observed in those where the abdominal nodal involvement was verified by histopathological biopsy.

    CONCLUSION: Diffuse large B-cell lymphomas patients with abdominal nodal disease had inferior outcome and more aggressive behaviour, reflected both in clinical and biological characteristics.

    Keywords
    BCL2, DLBCL, MYC, abdominal lymph node, survival
    National Category
    Clinical Laboratory Medicine
    Research subject
    Pathology; Pathology; Pathology
    Identifiers
    urn:nbn:se:uu:diva-400949 (URN)10.1111/ejh.13361 (DOI)000513873800007 ()31785002 (PubMedID)
    Available from: 2020-01-03 Created: 2020-01-03 Last updated: 2020-04-01Bibliographically approved
    4. PD-L1 and IDO1 are important immunosuppressive molecules in primary diffuse large B-cell lymphoma of the CNS
    Open this publication in new window or tab >>PD-L1 and IDO1 are important immunosuppressive molecules in primary diffuse large B-cell lymphoma of the CNS
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-403484 (URN)
    Available from: 2020-01-29 Created: 2020-01-29 Last updated: 2020-02-03Bibliographically approved
  • 3.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Guglielmo, Priscilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Brotzu General Hospital, Cagliari, Italy.
    Hollander, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Prognostic impact of abdominal lymph node involvement in diffuse large B-cell lymphoma2020In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 104, no 3, p. 207-213Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The prognostic value of site of nodal involvement in diffuse large B-cell lymphomas (DLBCL) is mainly unknown. We aimed to determine the prognostic significance of nodal abdominal involvement in relation to tumour cell markers and clinical characteristics of 249 DLBCL patients in a retrospective single-centre study.

    METHODS: Contrast-enhanced computed tomography (CT) of the abdomen and thorax revealed pathologically enlarged abdominal lymph nodes in 156 patients, while in 93 patients there were no pathologically enlarged lymph nodes in the abdomen. In 81 cases, the diagnosis of DLBCL was verified by histopathological biopsy obtained from abdominal lymph node.

    RESULTS: Patients with abdominal nodal disease had inferior lymphoma-specific survival (P = .04) and presented with higher age-adjusted IPI (P < .001), lactate dehydrogenase (P < .001) and more often advanced stage (P < .001), bulky disease (P < .001), B symptoms (P < .001), and double expression of MYC and BCL2 (P = .02) compared to patients without nodal abdominal involvement, but less often extranodal involvement (P < .02). The worst outcome was observed in those where the abdominal nodal involvement was verified by histopathological biopsy.

    CONCLUSION: Diffuse large B-cell lymphomas patients with abdominal nodal disease had inferior outcome and more aggressive behaviour, reflected both in clinical and biological characteristics.

  • 4.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hollander, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pandzic, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Mansouri, Larry
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Ednersson, Susanne Bram
    Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden.
    Andersson, Per-Ola
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden;Sodra Alvsborg Hosp Boras, Dept Med, Boras, Sweden.
    Hultdin, Magnus
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Fors, Maja
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Erlanson, Martin
    Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden.
    Degerman, Sofie
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Petersen, Helga Munch
    Copenhagen Univ Hosp, Dept Pathol, Rigshosp, Copenhagen, Denmark.
    Asmar, Fazila
    Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
    Gronbaek, Kirsten
    Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
    Enblad, Gunilla
    Uppsala Univ, Expt & Clin Oncol, Dept Immunol Genet & Pathol, Uppsala, Sweden.
    Cavelier, Lucia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma2019In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652Article in journal (Refereed)
    Abstract [en]

    The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

  • 5.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Laszlo, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Triumf, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hedström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Biosci & Nutr, Novum, Huddinge, Sweden..
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 9-10, p. 1126-1131Article in journal (Refereed)
    Abstract [en]

    Aim: To determine the prognostic significance of co-expression of MYC, BCL-2 and BCL-6 proteins in combination with other biomarkers and clinical characteristics within a population-based cohort of diffuse large B-cell lymphoma (DLBCL) patients uniformly treated with R-CHOP.

    Patients and methods: The immunohistochemical (IHC) expression of CD10, BCL-2, BCL-6, MUM1, MYC, CD5, CD30, Ki-67 and p53 was evaluated in a retrospective, population-based study comprising 188 DLBCL patients treated with R-CHOP and diagnosed in Sweden between 2002 and 2012.

    Results: Patients had a median age at diagnosis of 64 years (26-85 years) with a male:female ratio of 1.4:1. Approximately half (52%) of the patients presented with an International Prognostic Index (IPI) age adjusted (IPIaa)2. Median follow-up time was 51 months (range 0.4-158) and the five-year lymphoma-specific survival (LSS) was 76%, five-year overall survival (OS) was 65% and five-year progression-free survival (PFS) was 61%. A high Ki-67 value was found in 59% of patients, while p53 overexpression was detected in 12% of patients and MYC, BCL-2 and BCL-6 expression were detected in 42%, 55% and 74% of patients, respectively. IPIaa2 (p=0.002), Ki-6770% (p=0.04) and p53 overexpression50% (p=0.02) were associated with inferior LSS and OS. Co-expression of both MYC (>40%) and BCL-2 (>70%) proteins was detected in 27% of patients and correlated with a significantly inferior LSS (p=0.0002), OS (p=0.009) and PFS (p=0.03). In addition, triple expression of MYC, BCL-2 and BCL-6, also correlated with a significantly inferior LSS (p=0.02).

    Conclusion: Concurrent expression of MYC and BCL-2 proteins, as detected by IHC, was strongly associated with an inferior survival in DLBCL patients treated with R-CHOP. Other markers affecting survival were triple expression of MYC, BCL-2 and BCL-6, IPIaa, high Ki-67 and p53 overexpression.

  • 6.
    Abdulla, Maysaa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Laszlo, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Triumf, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Hedström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden.;Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden..
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Univ Uppsala Hosp, S-75185 Uppsala, Sweden..
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Core needle biopsies for the diagnosis of diffuse large B-cell lymphoma - a great concern for research2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 1, p. 106-109Article in journal (Refereed)
  • 7.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rollman Waara, Erik
    BioArctic Neurosci AB, Stockholm, Sweden.
    Möller, Christer
    BioArctic Neurosci AB, Stockholm, Sweden.
    Söderberg, Linda
    BioArctic Neurosci AB, Stockholm, Sweden.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. BioArctic Neuroscience AB, Stockholm, Sweden.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. BioArctic Neuroscience AB, Stockholm, Sweden.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury2018In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 28, no 4, p. 451-462Article in journal (Refereed)
    Abstract [en]

    Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n = 12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n = 5), to post-mortem tissue of neurologically intact (NI) subjects (n = 4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n = 4). The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to NI and iNPH controls (P < 0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n = 4) had increased levels of Aβ oligomers/protofibrils (P < 0.05) and of both N-terminally intact and truncated Aβ42 (P < 0.05) compared to APOE ε3/4-negative TBI patients (n = 8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers. We conclude that soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI.

  • 8.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Virhammar, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Cesarini, Kristina G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus2018In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, p. 1-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE The authors conducted a study to test if the cortical brain tissue levels of soluble amyloid beta (Aβ) reflect the propensity of cortical Aβ aggregate formation and may be an additional factor predicting surgical outcome following idiopathic normal pressure hydrocephalus (iNPH) treatment. METHODS Highly selective ELISAs (enzyme-linked immunosorbent assays) were used to quantify soluble Aβ40, Aβ42, and neurotoxic Aβ oligomers/protofibrils, associated with Aβ aggregation, in cortical biopsy samples obtained in patients with iNPH (n = 20), sampled during ventriculoperitoneal (VP) shunt surgery. Patients underwent pre- and postoperative (3-month) clinical assessment with a modified iNPH scale. The preoperative CSF biomarkers and the levels of soluble and insoluble Aβ species in cortical biopsy samples were analyzed for their association with a favorable outcome following the VP shunt procedure, defined as a ≥ 5-point increase in the iNPH scale. RESULTS The brain tissue levels of Aβ42 were negatively correlated with CSF Aβ42 (Spearman's r = -0.53, p < 0.05). The Aβ40, Aβ42, and Aβ oligomer/protofibril levels in cortical biopsy samples were higher in patients with insoluble cortical Aβ aggregates (p < 0.05). The preoperative CSF Aβ42 levels were similar in patients responding (n = 11) and not responding (n = 9) to VP shunt treatment at 3 months postsurgery. In contrast, the presence of cortical Aβ aggregates and high brain tissue Aβ42 levels were associated with a poor outcome following VP shunt treatment (p < 0.05). CONCLUSIONS Brain tissue measurements of soluble Aβ species are feasible. Since high Aβ42 levels in cortical biopsy samples obtained in patients with iNPH indicated a poor surgical outcome, tissue levels of Aβ species may be associated with the clinical response to shunt treatment.

  • 9. Adam, A
    et al.
    Robison, J
    Lu, J
    Jose, R
    Badran, N
    Vivas-Buitrago, T
    Rigamonti, D
    Sattar, A
    Omoush, O
    Hammad, M
    Dawood, M
    Maghaslah, M
    Belcher, T
    Carson, K
    Hoffberger, J
    Jusué Torres, I
    Foley, S
    Yasar, S
    Thai, Q A
    Wemmer, J
    Klinge, P
    Al-Mutawa, L
    Al-Ghamdi, H
    Carson, K A
    Asgari, M
    de Zélicourt, D
    Kurtcuoglu, V
    Garnotel, S
    Salmon, S
    Balédent, O
    Lokossou, A
    Page, G
    Balardy, L
    Czosnyka, Z
    Payoux, P
    Schmidt, E A
    Zitoun, M
    Sevestre, M A
    Alperin, N
    Baudracco, I
    Craven, C
    Matloob, S
    Thompson, S
    Haylock Vize, P
    Thorne, L
    Watkins, L D
    Toma, A K
    Bechter, Karl
    Pong, A C
    Jugé, L
    Bilston, L E
    Cheng, S
    Bradley, W
    Hakim, F
    Ramón, J F
    Cárdenas, M F
    Davidson, J S
    García, C
    González, D
    Bermúdez, S
    Useche, N
    Mejía, J A
    Mayorga, P
    Cruz, F
    Martinez, C
    Matiz, M C
    Vallejo, M
    Ghotme, K
    Soto, H A
    Riveros, D
    Buitrago, A
    Mora, M
    Murcia, L
    Bermudez, S
    Cohen, D
    Dasgupta, D
    Curtis, C
    Domínguez, L
    Remolina, A J
    Grijalba, M A
    Whitehouse, K J
    Edwards, R J
    Eleftheriou, A
    Lundin, F
    Fountas, K N
    Kapsalaki, E Z
    Smisson, H F
    Robinson, J S
    Fritsch, M J
    Arouk, W
    Garzon, M
    Kang, M
    Sandhu, K
    Baghawatti, D
    Aquilina, K
    James, G
    Thompson, D
    Gehlen, M
    Schmid Daners, M
    Eklund, A
    Malm, J
    Gomez, D
    Guerra, M
    Jara, M
    Flores, M
    Vío, K
    Moreno, I
    Rodríguez, S
    Ortega, E
    Rodríguez, E M
    McAllister, J P
    Guerra, M M
    Morales, D M
    Sival, D
    Jimenez, A
    Limbrick, D D
    Ishikawa, M
    Yamada, S
    Yamamoto, K
    Junkkari, A
    Häyrinen, A
    Rauramaa, T
    Sintonen, H
    Nerg, O
    Koivisto, A M
    Roine, R P
    Viinamäki, H
    Soininen, H
    Luikku, A
    Jääskeläinen, J E
    Leinonen, V
    Kehler, U
    Lilja-Lund, O
    Kockum, K
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Riklund, K
    Söderström, L
    Hellström, P
    Laurell, K
    Kojoukhova, M
    Sutela, A
    Vanninen, R
    Vanha, K I
    Timonen, M
    Rummukainen, J
    Korhonen, V
    Helisalmi, S
    Solje, E
    Remes, A M
    Huovinen, J
    Paananen, J
    Hiltunen, M
    Kurki, M
    Martin, B
    Loth, F
    Luciano, M
    Luikku, A J
    Hall, A
    Herukka, S K
    Mattila, J
    Lötjönen, J
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Jurjević, I
    Miyajima, M
    Nakajima, M
    Murai, H
    Shin, T
    Kawaguchi, D
    Akiba, C
    Ogino, I
    Karagiozov, K
    Arai, H
    Reis, R C
    Teixeira, M J
    Valêncio, C G
    da Vigua, D
    Almeida-Lopes, L
    Mancini, M W
    Pinto, F C G
    Maykot, R H
    Calia, G
    Tornai, J
    Silvestre, S S S
    Mendes, G
    Sousa, V
    Bezerra, B
    Dutra, P
    Modesto, P
    Oliveira, M F
    Petitto, C E
    Pulhorn, H
    Chandran, A
    McMahon, C
    Rao, A S
    Jumaly, M
    Solomon, D
    Moghekar, A
    Relkin, N
    Hamilton, M
    Katzen, H
    Williams, M
    Bach, T
    Zuspan, S
    Holubkov, R
    Rigamonti, A
    Clemens, G
    Sharkey, P
    Sanyal, A
    Sankey, E
    Rigamonti, K
    Naqvi, S
    Hung, A
    Schmidt, E
    Ory-Magne, F
    Gantet, P
    Guenego, A
    Januel, A C
    Tall, P
    Fabre, N
    Mahieu, L
    Cognard, C
    Gray, L
    Buttner-Ennever, J A
    Takagi, K
    Onouchi, K
    Thompson, S D
    Thorne, L D
    Tully, H M
    Wenger, T L
    Kukull, W A
    Doherty, D
    Dobyns, W B
    Moran, D
    Vakili, S
    Patel, M A
    Elder, B
    Goodwin, C R
    Crawford, J A
    Pletnikov, M V
    Xu, J
    Blitz, A
    Herzka, D A
    Guerrero-Cazares, H
    Quiñones-Hinojosa, A
    Mori, S
    Saavedra, P
    Treviño, H
    Maitani, K
    Ziai, W C
    Eslami, V
    Nekoovaght-Tak, S
    Dlugash, R
    Yenokyan, G
    McBee, N
    Hanley, D F
    Abstracts from Hydrocephalus 2016.2017In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 14, no Suppl 1, article id 15Article in journal (Refereed)
  • 10.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Popova, Svetlana N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Departmen of Pathology, Uppsala University hospital.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Expression of CMV protein pp65 in cutaneous malignant melanoma.2019In: PLoS ONE, E-ISSN 1932-6203, Vol. 14, no 10, article id e0223854Article in journal (Refereed)
    Abstract [en]

    Human cytomegalovirus (CVM) has been detected by immunohistochemistry (IHC) in brain tumours; however, whether CMV antigen is seen in melanomas has not yet been elucidated. Applying IHC, melanoma tissue was assessed for the expression of pp65, a tegument protein of CMV. Two cohorts were available, cohort-I and II, the latter included also related metastasis. In addition to IHC, in situ hybridisation (ISH) was carried out to assess whether CMV related genetic sequences were detectable in a subset of cases. Seventy per cent of the 142 cases in cohort-I and 50% of the 37 cases in cohort-II displayed immunoreactivity (IR). In both cohorts, the IHC outcome correlated with T-stage (Cohort I: Spearman 0.22, p = 0.01, Cohort II: Fisher exact text 0.04). In 30 of cohort-II cases, when IHC staining was carried out on both the primary tumour and the corresponding metastasis, no change in IR was noted in 53%; in 20%, the IR was lower and in 27% higher in the metastasis when compared with the primary tumour. These results were significant (Fisher exact test 0.03). Applying ISH technique on four tumour cases with detectable pp65 protein, CMV related genetic sequence was not detected. Here, we demonstrate, congruent with observations published for brain tumours, that the protein pp65 is indeed observed in substantial number of melanoma cases with IHC; however, no signal was detected with ISH technique. These findings are in line with previously reported studies, demonstrating that the role of CMV in tumours is still debatable.

  • 11.
    Agnarsdóttir, Margrét
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Päären, Helen
    Vassilaki, Ismini
    The impact of standardized care pathway on reporting time for invasive melanoma - results from one pathology department in Sweden.2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 4, p. 260-264Article in journal (Refereed)
    Abstract [en]

    Background: Standardized care pathway (SCP) was introduced by the Swedish health authorities to eliminate unwanted delay in the diagnostics of cancer patients; for melanoma, SCP started in 2016. The aim of this study was to investigate the impact of SCP on reporting time for invasive melanomas.Materials and methods: Information on reporting time was collected on all samples handled according to the SCP and on all invasive melanomas diagnosed in 2016-2018 at the Department of Clinical Pathology, Akademiska University Hospital, Uppsala, Sweden.Results: During the study period, 205 samples were handled according to the SCP, resulting in 53 cases (26%) diagnosed with invasive melanomas. A total of 301 invasive melanomas from 286 patients were diagnosed during the study period; 67 (22%) were submitted as SCP, 36 (12%) as a general priority case, and 198 (66%) as non-priority. The reporting time for the SCP cases was 8 days, for general priority cases 6 days, and for non-priority cases it was 24 days. The reporting time increased from 18 to 31 days for the non-priority cases and from 15 to 25 days for all cases with invasive melanomas during the study period.Conclusion: This study demonstrates prolonged reporting times for invasive melanomas since the implementation of SCP. This is probably caused by the crowd-out effect of the SCP samples, limited personnel resources, and inaccuracy of the clinical diagnosis. SCP might therefore be a suboptimal method to shorten reporting times for invasive melanomas.

  • 12.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Minimal neuropathologic diagnosis for brain banking in the normal middle-aged and aged brain and in neurodegenerative disorders.2018In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 150, p. 131-141, article id B978-0-444-63639-3.00010-4Article in journal (Refereed)
    Abstract [en]

    Research on human brain diseases is currently often conducted on cell cultures and animals. Several questions however can only be addressed by studying human postmortem brain tissue. However, brain tissue obtained postmortem almost always displays pathology that is often related to the aging phenomenon. Thus, in order to be certain that the answers obtained are reliable, a systematic and thorough assessment of the brain tissue to be studied should be carried out. We are currently aware of several protein alterations that are found in middle-aged and aged brains that are obtained from neurologically unimpaired subjects. The most common alteration is hyperphosphorylation of τ, observed in both neurons and glial cells, in certain brain regions, followed by β-amyloid aggregation in the neuropil and vessel walls. Less common protein alterations are those noted for α-synuclein and Tar DNA-binding protein 43. It is noteworthy that these alterations, when found in excess, are diagnostic for various neurodegenerative diseases, such as Alzheimer disease, Pick disease, progressive supranuclear palsy, corticobasal degeneration, Parkinson disease, Lewy body dementia, and frontotemporal lobar degeneration. Since 1990, the neuropathology community has been aware that these protein alterations tend to progress in an orderly neuroanatomically defined manner and have thus designed a method to define a stage or a phase of the protein alteration. The neuropathology community has defined an initiation site, or neuroanatomic area that they presume the alteration originates from, and defined a presumed pattern of progression from the initiation site to other brain areas. Thus a reliable and reproducible description of each case regarding these alterations can be achieved. In addition to the above alterations, the brain tissue is also prone to various vascular alterations that should be registered as seen or not seen even if the significance of these alterations is still unclear.

  • 13.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Techniques in neuropathology.2017In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 145, p. 3-7, article id B978-0-12-802395-2.00001-8Article in journal (Refereed)
    Abstract [en]

    The primary objective for a neuropathologist is the characterization of the tissue that is being assessed and thus all available techniques ranging from naked-eye examination to assessment of genetic/epigenetic characteristics are currently applied. What is observed in the tissue obtained from a diseased subject is compared with what is observed in a healthy individual and, based on the outcome, neuropathologic definitions of diseases are constructed. Thus, with the naked eye a neuropathologist can confirm that a hemorrhage is observed in the brain, by histologic examination that the hemorrhage is caused by alterations in the brain vessels and, since 1954, applying Congo red dye neuropathologists have been able to state that congophilic angiopathy is detected. Since 1984, applying immunohistochemical methods neuropathologists have been able to verify that the protein seen in the vessel walls is β-amyloid and by genetic/epigenetic analysis eventual mutation or modifications of genome might be detected. The development of new techniques is staggering and throughout this book the authors have listed techniques currently applied while assessing various disease-related hallmark lesions. In the following a general summary of techniques applied is given.

  • 14.
    Alafuzoff, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hartikainen, Päivi
    Alpha-synucleinopathies.2017In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 145, p. 339-353, article id B978-0-12-802395-2.00024-9Article in journal (Refereed)
    Abstract [en]

    A neurodegenerative disorder displaying an altered α-synuclein (αS) in the brain tissue is called α-synucleinopathy (αS-pathy) and incorporates clinical entities such as Parkinson disease (PD), PD with dementia, dementia with Lewy bodies, and multiple-system atrophy. Neuroradiologic techniques visualizing αS pathology in the brain or assays of αS in the cerebrospinal fluid or blood are probably available and will be implemented in the near future but currently the definite diagnosis of αS-pathy relies on a postmortem examination of the brain. Since the 1980s immunohistochemical technique based on the use of antibodies directed to proteins of interest has become a method of choice for neuropathologic diagnosis. Furthermore, since the 1990s it has been acknowledged that progressions of most neurodegenerative pathologies follow a certain predictable time-related neuroanatomic distribution. Currently, for Lewy body disease, two staging techniques are commonly used: McKeith and Braak staging. Thus, the neuropathologic diagnosis of a αS-pathy is based on detection of altered αS in the tissue and registration of the neuroanatomic distribution of this alteration in the brain. The clinicopathologic correlation is not absolute due to the quite frequent observation of incidental and concomitant αS pathology.

  • 15.
    Alafuzoff, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Kovacs, Gabor G
    Comorbidities.2017In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 145, p. 573-577, article id B978-0-12-802395-2.00036-5Article in journal (Refereed)
    Abstract [en]

    The term comorbidities or mixed pathologies is used when brain tissue, a surgical sample, or postmortem brain displays a mixture of protein alterations or other pathologies. Most of the alterations when seen in sufficient extent are considered causative, are related to a certain clinical phenotype, i.e., when hyperphosphorylated τ (HPτ) is observed in occipital cortex concomitant with β-amyloid (Aβ), the diagnosis is Alzheimer disease (AD). When HPτ is observed in hippocampal structures in a subject with extensive and widespread α-synuclein pathology, a Lewy body disease (LBD), the HPτ pathology is considered as a concomitant alteration. There are numerous reports indicating that when "concomitant" pathologies are seen in a subject with certain neurodegenerative diseases, the clinical phenotype might be altered. In addition there are those cases where many alterations are seen in a sparse extent, but jointly they lead to a clinical syndrome. Thus today it is not sufficient to confirm a certain pathology to be seen, i.e., AD- or LBD-related; in addition the concomitant aging-related alterations have to be looked for.

  • 16.
    Alafuzoff, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Popova, Svetlana N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Wanders, Alkwin
    Department of Clinical Pathology and Cytology, Umea University Hospital, Umea, Sweden.
    Veress, Bela
    Department of Clinical Pathology and Cytology, Skane University Hospital, Malmo, Sweden.
    Neuronal Protein Alteration in Enteric Dysmotility Syndrome2016In: Journal of Alzheimer’s Disease & Parkinsonism, ISSN 2161-0460, Vol. 6, no 1, article id 1000212Article in journal (Other academic)
  • 17.
    Albertsson-Lindblad, Alexandra
    et al.
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Kolstad, Arne
    Oslo Univ Hosp, Dept Oncol, Oslo, Norway..
    Laurell, Anna
    Univ Uppsala Hosp, Dept Oncol, Uppsala, Sweden..
    Raty, Riikka
    Helsinki Univ Hosp, Dept Hematol, Helsinki, Finland..
    Gronbaek, Kirsten
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Sundberg, Jan
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Ralfkiaer, Elisabeth
    Rigshosp, Dept Pathol, Copenhagen, Denmark..
    Karjalainen-Lindsberg, Marja-Liisa
    Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland..
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; and..
    Ehinger, Mats
    Univ Lund Hosp, Dept Pathol Cytol, Lund, Sweden..
    Geisler, Christian
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Jerkeman, Mats
    Skane Univ Hosp, Dept Oncol, SE-22185 Lund, Sweden..
    Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, no 14, p. 1814-1820Article in journal (Refereed)
    Abstract [en]

    For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.

  • 18.
    Amini, Rose-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hollander, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Laszlo, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Eriksson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Gustafsson, Kristin Ayoola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Loskog, Angelica S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Lokon Pharma, AB,Uppsala, Sweden.
    Thörn, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Altered profile of immune regulatory cells in the peripheral blood of lymphoma patients2019In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 316Article in journal (Refereed)
    Abstract [en]

    Background: Regulatory immune cells may modulate the lymphoma microenvironment and are of great interest due to the increasing prevalence of treatment with immunotherapies in lymphoma patients. The aim was to explore the composition of different immune regulatory cell subsets in the peripheral blood of newly diagnosed lymphoma patients in relation to treatment outcome. Methods: Forty-three newly diagnosed patients with lymphoma were included in the study; 24 with high-grade B-cell lymphoma (HGBCL) and 19 with classical Hodgkin lymphoma (cHL). Peripheral blood was prospectively collected and immune regulatory cells were identified by multi-color flow cytometry and analyzed in relation to healthy blood donors and clinical characteristics and outcome. Results: The percentage of CD3-positive T-cells was lower (p=0.03) in the peripheral blood of lymphoma patients at diagnosis compared to healthy blood donors regardless of lymphoma subtype, although statistically, neither the percentage of monocytes (p=0.2) nor the T-cell/monocyte ratio (p=0.055) differed significantly. A significant decrease in the percentage of a subset of regulatory NK cells (CD7(+)/CD3(-)/CD56(bright)/CD16(dim/-)) was identified in the peripheral blood of lymphoma patients compared to healthy blood donors (p=0.003). Lymphoma patients also had more granulocytic myeloid-derived suppressor cells (MDSCs) (p=0.003) compared to healthy blood donors, whereas monocytic MDSCs did not differ significantly (p=0.07). A superior disease-free survival was observed for cHL patients who had an increase in the percentage of granulocytic MDSCs (p=0.04). Conclusions: An altered profile of immune cells in the peripheral blood with a decrease in T-cells and regulatory NK-cells was observed in newly diagnosed lymphoma patients. CHL patients with higher percentages of regulatory NK cells and higher percentages of granulocytic MDSCs might have a better outcome, although the number of patients was low.

  • 19.
    Amini, Rose-Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    [Core needle biopsies for lymphoma diagnosis seriously affect diagnostics, treatment development and research].2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, article id EMDHArticle in journal (Refereed)
    Abstract [sv]

    Core needle biopsies for lymphoma diagnosis seriously affect diagnostics, treatment development and research Core needle biopsies (CNBs) are widely used in clinical diagnostic labs to aid in the diagnosis of malignant lymphomas and in latter years their use is increasing. CNBs provide a rapid method for obtaining tumour material and may be beneficial when the affected lymph nodes are located deep in the abdominal cavity or mediastinum and surgical excisional biopsies may be difficult to perform. However, according to the Swedish Haematopathology Quality and Standardization Committee, CNBs are insufficient for lymphoma diagnostic purposes and the guidelines state that material from surgical excisional biopsies are mandatory in order to obtain a robust histopathological evaluation of the lymph node architecture, cellular composition and growth pattern. Surgical excision biopsies also ensure that adequate material is available if additional molecular analyses should be required and also to facilitate future research.

  • 20.
    Anan, Intissar
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Bång, Joakim
    Umea Univ, Dept Surg & Perioperat Sci Orthopaed, Umea, Sweden.
    Lundgren, Hans-Erik
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Wixner, Jonas
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    A case report of osteoarthritis associated with hereditary transthyretin amyloidosis ATTRV30M2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, no Suppl. 1, p. 29-30Article in journal (Refereed)
  • 21.
    Andersson, Sandra
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Fagerberg, Linn
    Hallstrom, Bjorn M.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Danielsson, Angelika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Uhlen, Mathias
    Asplund, Anna
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, p. e115911-Article in journal (Refereed)
    Abstract [en]

    Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.

  • 22.
    Antonodimitrakis, Pantelis Clewemar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Olofsson, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study2017In: International Journal of Endocrine Oncology, Vol. 4, no 1, p. 9-22Article in journal (Refereed)
    Abstract [en]

    Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.

  • 23.
    Aresdahl, Alexander
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Lindell, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Dukic, Milena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Congenital granular cell epulis: a case report2015In: Oral and Maxillofacial Surgery Cases, ISSN 2214-5419, Vol. 1, no 1, p. 8-11Article in journal (Refereed)
    Abstract [en]

    Congenital granular cell epulis (CGCE) is an uncommon benign lesion found in newborns. It has predominance for females with an 8:1 ratio in relation to males and is exclusively encountered in the oral cavity. The most affected oral site is located around the canine/incisor region of the maxillary alveolar ridge, where the lesion arises from the soft tissue as a solitary pedunculated mass. CGCE's histogenesis remains obscure and controversial. We present a rare case of 2 separate CGCE lesions adjacent to each other measuring 23 × 18 × 10 and 15 × 10 mm, positioned facially on the right maxillary alveolar process. The patient, a 2-day-old female newborn, did not experience any serious difficulty regarding breathing or deglutition. Complete surgical excision was the treatment of choice in this case, and the procedure was performed under both general and local anesthesia. Histologic and immunohistochemical analysis confirmed the diagnosis of CGCE. The patient showed satisfactory postoperative healing and excellent health at both the 10-day recall appointment and the 6-month follow-up.

  • 24. Asa, Sylvia L
    et al.
    Asioli, Sofia
    Bozkurt, Suheyla
    Casar Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Chinezu, Laura
    Comunoglu, Nil
    Cossu, Giulia
    Cusimano, Michael
    Delgrange, Etienne
    Earls, Peter
    Ezzat, Shereen
    Gazioglu, Nurperi
    Grossman, Ashley
    Guaraldi, Federica
    Hickman, Richard A
    Ikeda, Hidetoshi
    Jaffrain-Rea, Marie-Lise
    Karavitaki, Niki
    Kraljević, Ivana
    La Rosa, Stefano
    Manojlović-Gačić, Emilija
    Maartens, Niki
    McCutcheon, Ian E
    Messerer, Mahmoud
    Mete, Ozgur
    Nishioka, Hiroshi
    Oz, Buge
    Pakbaz, Sara
    Pekmezci, Melike
    Perry, Arie
    Reiniger, Lilla
    Roncaroli, Federico
    Saeger, Wolfgang
    Söylemezoğlu, Figen
    Tachibana, Osamu
    Trouillas, Jacqueline
    Turchini, John
    Uccella, Silvia
    Villa, Chiara
    Yamada, Shozo
    Yarman, Sema
    Pituitary neuroendocrine tumors (PitNETs): nomenclature evolution, not clinical revolution.2019In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403Article in journal (Refereed)
  • 25.
    Avenel, Christophe
    et al.
    CADESS Med AB, Uppsala, Sweden.
    Tolf, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden..
    Carlbom, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. CADESS Med AB, Uppsala, Sweden.
    Glandular Segmentation of Prostate Cancer: An Illustration of How the Choice of Histopathological Stain Is One Key to Success for Computational Pathology2019In: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 7, article id 125Article in journal (Refereed)
    Abstract [en]

    Digital pathology offers the potential for computer-aided diagnosis, significantly reducing the pathologists' workload and paving the way for accurate prognostication with reduced inter-and intra-observer variations. But successful computer-based analysis requires careful tissue preparation and image acquisition to keep color and intensity variations to a minimum. While the human eye may recognize prostate glands with significant color and intensity variations, a computer algorithm may fail under such conditions. Since malignancy grading of prostate tissue according to Gleason or to the International Society of Urological Pathology (ISUP) grading system is based on architectural growth patterns of prostatic carcinoma, automatic methods must rely on accurate identification of the prostate glands. But due to poor color differentiation between stroma and epithelium from the common stain hematoxylin-eosin, no method is yet able to segment all types of glands, making automatic prognostication hard to attain. We address the effect of tissue preparation on glandular segmentation with an alternative stain, Picrosirius red-hematoxylin, which clearly delineates the stromal boundaries, and couple this stain with a color decomposition that removes intensity variation. In this paper we propose a segmentation algorithm that uses image analysis techniques based on mathematical morphology and that can successfully determine the glandular boundaries. Accurate determination of the stromal and glandular morphology enables the identification of the architectural pattern that determine the malignancy grade and classify each gland into its appropriate Gleason grade or ISUP Grade Group. Segmentation of prostate tissue with the new stain and decomposition method has been successfully tested on more than 11000 objects including well-formed glands (Gleason grade 3), cribriform and fine caliber glands (grade 4), and single cells (grade 5) glands.

  • 26.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala Univ Hosp, Dept Clin Genet, Uppsala, Sweden.
    Kättström, Magdalena
    Orebro Univ Hosp, Dept Med, Sect Hematol, Orebro, Sweden.
    Rossing, Maria
    Copenhagen Univ Hosp, Ctr Genom Med, Copenhagen, Denmark.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Refractory chronic "ITP": When platelet size matters2018In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 6, no 9, p. 1779-1780Article in journal (Refereed)
    Abstract [en]

    Key Clinical Message Inherited conditions associated with thrombocytopenia should be included in the differential diagnosis of young patients with refractory immune thrombocytopenia (ITP), even in the absence of a positive family history. Early identification of such conditions is of vital importance in order to reach the right diagnosis and avoid unnecessary or even harmful medication.

  • 27.
    Bellotti, Vittorio
    et al.
    UCL, Div Med, Ctr Amyloidosis & Acute Phase Prot, Wolfson Drug Discovery Unit, London, England;Univ Pavia, Inst Biochem, Dept Mol Med, Pavia, Italy.
    Merlini, Giampaolo
    Univ Pavia, Fdn IRCCS Policlin San Matteo, Amyloidosis Res & Treatment Ctr, Biotechnol Res Labs,Dept Mol Med, Pavia, Italy.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Biographical item "Robert Kisilevsky, Md, Phd, 1937-2019 In Memoriam", in Amyloid: The Journal of Protein Folding Disorders Volume 26, 2019, Issue 4, p 179.2019Other (Other (popular science, discussion, etc.))
  • 28.
    Benson, Merrill D.
    et al.
    Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA.
    Buxbaum, Joel N.
    Scripps Res Inst, Dept Mol Med, La Jolla, CA USA.
    Eisenberg, David S.
    Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA USA.
    Merlini, Giampaolo
    Univ Pavia, Amyloid Res & Treatment Ctr, Pavia, Italy; IRCCS Policlin San Matteo, Pavia, Italy.
    Saraiva, Maria J. M.
    Univ Porto, Inst Mol & Cellular Biol, Amyloid Unit, Porto, Portugal.
    Sekijima, Yoshiki
    Shinshu Univ, Sch Med, Dept Med Neurol & Rheumatol, Matsumoto, Nagano, Japan.
    Sipe, Jean D.
    Boston Univ, Sch Med, Dept Biochem, Boston, MA USA.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 4, p. 215-219Article in journal (Refereed)
    Abstract [en]

    The nomenclature committee of the International Society of Amyloidosis (ISA) meets every second year to discuss and formulate recommendations. The conclusions from the discussion at the XVI International Symposium on Amyloidosis in Kumamoto, Japan, 25–29 March 2018 and afterwards are summarized in this Nomenclature Article. From having recommended the use of the designation “amyloid fibril” for in vivo material only, ISA’s nomenclature committee now accepts its use more broadly following the international scientific literature. However, it is important always to stress the origin of the β-fibrils in order to avoid misunderstanding. Given the more broad use of the word “amyloid” several classes of amyloid fibrils may be distinguished. For the medical in vivo situation, and to be included in the amyloid nomenclature list, “amyloid” still means mainly extracellular tissue deposits of protein fibrils, recognized by specific properties, such as green-yellow birefringence after staining with Congo red. It should also be underlined that in vivo amyloid fibrils, in addition to the main protein contain associated compounds, particularly serum amyloid P-component (SAP) and proteoglycans, mainly heparan sulfate proteoglycan. With this definition there are presently 36 human amyloid proteins of which 14 appear only associated with systemic amyloidosis and 19 as localized forms. Three proteins can occur both as localized and systemic amyloidosis. Strictly intracellular aggregates are not included in this list.

  • 29.
    Berglund, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Kinch, Amelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Edman, Elin
    Halmstad Hospital.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Expression of Intratumoral Forkhead Box Protein 3 in Posttransplant Lymphoproliferative Disorders: Clinical Features and Survival Outcomes2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 5, p. 1036-1042Article in journal (Refereed)
    Abstract [en]

    Background. The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.

    Methods. Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records.

    Results. Based on a cutoff level of 29 FoxP3+ cells per mm2, most (80%) of the PTLDs were FoxP3-. Forty-seven of 74 PTLDs displayed no FoxP3+ cells at all. The frequency of FoxP3+ cells did not influence median overall survival. The FoxP3- PTLDs were more frequently of T-cell phenotype (P=0.04), located at the graft (P=0.03), occurred earlier after transplantation (P=0.04), were more likely to develop in lung recipients (P=0.04), and in patients that had received anti T-cell globulin as induction therapy (P=0.02). The FoxP3+ PTLDs were associated with hepatitis C seropositivity (P=0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity.

    Conclusion. Our findings suggest that intratumoral FoxP3+ Tregs do not influence survival in patients with PTLD. FoxP3+ Tregs are rare in PTLD, possibly because of heavy immunosuppression.

  • 30.
    Bergman, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and 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.
    Fagerberg, Linn
    KTH Royal Inst Technol, Sci Life Lab, SE-17121 Stockholm, Sweden.
    Hallström, Björn M.
    KTH Royal Inst Technol, Sci Life Lab, SE-17121 Stockholm, Sweden.
    Djureinovic, Dijana
    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.
    Uhlén, Mathias
    KTH Royal Inst Technol, Sci Life Lab, SE-17121 Stockholm, Sweden.
    Ponten, Fredrik
    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.
    The human adrenal gland proteome defined by transcriptomics and antibody-based profiling2017In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 158, no 2, p. 239-251Article in journal (Refereed)
    Abstract [en]

    The adrenal gland is a composite endocrine organ with vital functions that include the synthesis and release of glucocorticoids and catecholamines. To define the molecular landscape that underlies the specific functions of the adrenal gland, we combined a genome-wide transcriptomics approach based on mRNA sequencing of human tissues with immunohistochemistry-based protein profiling on tissue microarrays. Approximately two-thirds of all putative protein coding genes were expressed in the adrenal gland and the analysis identified 253 genes with an elevated pattern of expression in the adrenal gland, with only 37 genes showing a markedly higher expression level (>5-fold) in the adrenal gland compared to 31 other normal human tissue types analyzed. The analyses allowed for an assessment of the relative expression levels for well-known proteins involved in adrenal gland function, but also identified previously poorly characterized proteins in the adrenal cortex, such as FERM domain containing 5 (FRMD5) and protein NOV homolog (NOV). In summary, we provide a global analysis of the adrenal gland transcriptome and proteome, with a comprehensive list of genes with elevated expression in the adrenal gland and spatial information with examples of protein expression patterns for corresponding proteins. These genes and proteins constitute important starting points for an improved understanding of the normal function and pathophysiology of the adrenal glands.

  • 31.