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Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. (Patrick Micke)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. (Patrick Micke)ORCID iD: 0000-0002-5294-7808
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.ORCID iD: 0000-0001-5611-1015
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. (Patrick Micke)
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2019 (English)In: Clinical Lung Cancer, ISSN 1525-7304, E-ISSN 1938-0690, Vol. 20, no 4, p. 258-262.e1Article in journal (Refereed) Published
Abstract [en]

Programmed cell death ligand 1 (PD-L1) expression within the same lung cancer tissue is variable. In this study we evaluated if the PD-L1 expression on small biopsy specimens represent the PD-L1 status of the corresponding resection specimen. Our results indicate a relative good agreement between biopsy and surgical specimens, with a discordance in approximately 10% of the cases. Background: The immunohistochemical analysis of programmed cell death ligand 1 (PD-L1) expression in tumor tissue of non-small-cell lung cancer patients has now been integrated in the diagnostic workup. Analysis is commonly done on small tissue biopsy samples representing a minimal fraction of the whole tumor. The aim of the study was to evaluate the correlation of PD-L1 expression on biopsy specimens with corresponding resection specimens. Materials and Methods: In total, 58 consecutive cases with preoperative biopsy and resected tumor specimens were selected. From each resection specimen 2 tumor cores were compiled into a tissue microarray (TMA). Immunohistochemical staining with the antibody SP263 was performed on biopsy specimens, resection specimens (whole sections), as well as on the TMA. Results: The proportion of PD-L1-positive stainings were comparable between the resection specimens (48% and 19%), the biopsies (43% and 17%), and the TMAs (47% and 14%), using cutoffs of 1% and 50%, respectively (P > .39 all comparisons). When the resection specimens were considered as reference, PD-L1 status differed in 16%/5% for biopsies and in 9%/9% for TMAs (1%/50% cutoff). The sensitivity of the biopsy analysis was 79%/82% and the specificity was 90%/98% at the 1%/50% cutoff. The Cohens kappa value for the agreement between biopsy and tumor. was 0.70 at the 1% cutoff and 0.83 at the 50% cutoff. Conclusion: The results indicate a moderate concordance between the analysis of biopsy and whole tumor tissue, resulting in misclassification of samples in particular when the lower 1% cutoff was used. Clinicians should be aware of this uncertainty when interpreting PD-L1 reports for treatment decisions.

Place, publisher, year, edition, pages
2019. Vol. 20, no 4, p. 258-262.e1
Keywords [en]
Checkpoint inhibitors, Nivolumab, PD-1, PD-L1, Pembrolizumab
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-390976DOI: 10.1016/j.cllc.2019.02.012ISI: 000475296800018PubMedID: 30926355OAI: oai:DiVA.org:uu-390976DiVA, id: diva2:1343487
Funder
Swedish Cancer SocietyAvailable from: 2019-08-16 Created: 2019-08-16 Last updated: 2023-12-04Bibliographically approved
In thesis
1. Improving the diagnostic armamentarium of lung cancer
Open this publication in new window or tab >>Improving the diagnostic armamentarium of lung cancer
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lung cancer is the leading cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) constituting 85% of cases. The introduction of immunotherapies and targeted therapies have dramatically improved the prognosis and outcome for a subset of patients, and stressed the development of diagnostic tools for effective patient selection. This thesis addresses different aspects of current and future diagnostic strategies in NSCLC patients.

In Paper I, an immunohistochemical assay targeting the neurotropic tropomyosin receptor kinase (NTRK) was evaluated on tissue microarrays (TMAs) from a well-characterized NSCLC cohort. Although a few cases showed positive staining, none were positive in the reference molecular testing, highlighting the rarity of this targetable aberration and underscoring the value of cost-effective screening methods.

In Paper II, paired patient samples (biopsy, TMA, and surgical specimen) were evaluated regarding the immunohistochemical staining for PD-L1. The results indicated a strong correlation between the PD-L1 expression on biopsy and TMA compared with the tumor whole slide, suggesting that tumor heterogeneity has minor relevance for PD-L1 evaluation.

In Paper III, paired tissue samples (biopsy, TMA, and surgical specimen) were evaluated regarding infiltrating CD3+ immune cells. Only weak correlation was found between the biopsies and tumor whole slide, while the agreement between the whole slide and TMA was higher. These results question the use of biopsies for immune cell quantification, while supporting the TMA as a reliable tool in cancer research.

In Paper IV, the amount and distribution of tertiary lymphoid structures (TLS) was annotated on scanned tumor whole slides. TLS were present in most of the tumors and correlated with the abundance of specific immune cell subsets. Higher number of TLS were associated with longer survival, particularly in adenocarcinomas. High tumor mutational burden was associated with higher numbers of periphery TLS. These results provide a rationale for using TLS metrics as a diagnostic marker for NSCLC patients undergoing surgical resection.

In summary, this thesis addresses challenges in prognostic and predictive lung cancer diagnostics in the areas of targeted therapy and immunotherapy. The results provide crucial insights into tumor heterogeneity that may impact clinical decision-making and aid scientists in selecting appropriate tissue sources for translational and clinical cancer research.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2024. p. 48
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2000
Keywords
lung cancer, tissue microarray, immunohistochemistry, targeted therapy, immunotherapy, checkpoint inhibitors, immune microenvironment, prognosis, biomarkers, immune cells.
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-517163 (URN)978-91-513-1984-1 (ISBN)
Public defence
2024-02-02, Rudbecksalen, Rudbecklaboratoriet, Dag Hammasjölds väg 20, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2024-01-11 Created: 2023-12-04 Last updated: 2024-01-11

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Elfving, HedvigMattsson, Johanna Sofia MargaretaLindskog, CeciliaBackman, MaxMenzel, UweMicke, Patrick

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