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Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. (Patrick Micke)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. (Patrick Micke)ORCID-id: 0000-0002-5294-7808
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.ORCID-id: 0000-0001-5611-1015
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. (Patrick Micke)
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2019 (Engelska)Ingår i: Clinical Lung Cancer, ISSN 1525-7304, E-ISSN 1938-0690, Vol. 20, nr 4, s. 258-262.e1Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2019. Vol. 20, nr 4, s. 258-262.e1
Nyckelord [en]
Checkpoint inhibitors, Nivolumab, PD-1, PD-L1, Pembrolizumab
Nationell ämneskategori
Cancer och onkologi Klinisk laboratoriemedicin
Forskningsämne
Patologi
Identifikatorer
URN: urn:nbn:se:uu:diva-390976DOI: 10.1016/j.cllc.2019.02.012ISI: 000475296800018PubMedID: 30926355OAI: oai:DiVA.org:uu-390976DiVA, id: diva2:1343487
Forskningsfinansiär
CancerfondenTillgänglig från: 2019-08-16 Skapad: 2019-08-16 Senast uppdaterad: 2023-12-04Bibliografiskt granskad
Ingår i avhandling
1. Improving the diagnostic armamentarium of lung cancer
Öppna denna publikation i ny flik eller fönster >>Improving the diagnostic armamentarium of lung cancer
2024 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2024. s. 48
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2000
Nyckelord
lung cancer, tissue microarray, immunohistochemistry, targeted therapy, immunotherapy, checkpoint inhibitors, immune microenvironment, prognosis, biomarkers, immune cells.
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:uu:diva-517163 (URN)978-91-513-1984-1 (ISBN)
Disputation
2024-02-02, Rudbecksalen, Rudbecklaboratoriet, Dag Hammasjölds väg 20, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2024-01-11 Skapad: 2023-12-04 Senast uppdaterad: 2024-01-11

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

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