Dataset Information

PD-L1 Immunohistochemistry Assay Concordance in Urothelial Carcinoma of the Bladder and Hypopharyngeal Squamous Cell Carcinoma.

ABSTRACT: Programmed death ligand-1 (PD-L1) immunohistochemistry is used to guide treatment decisions regarding the use of checkpoint immunotherapy in the management of urothelial carcinoma of the bladder and hypopharyngeal (HP) squamous cell carcinoma. With increasing PD-L1 testing options, a need has arisen to assess the analytical comparability of diagnostic assays in order to develop a more sustainable testing strategy. Using tissue microarrays, PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was manually scored in 197 cases and 27 cases of bladder and HP cancer, respectively. Three commercial kits (Ventana SP263, Ventana SP142, Dako 22C3) and 1 platform-independent test (Cell Signalling Technologies E1L3N) were utilized. Across the 3 commercially available clones, 14% and 74% of urothelial carcinomas were positive and negative, respectively, whereas 7% and 78% of HP carcinomas were positive and negative, respectively. Twelve percent of bladder and 15% HP cases showed discrepant PD-L1 classification results. Regardless of the scoring algorithm used, E1L3N provided comparable PD-L1 staining results. Fleiss' kappa and intraclass correlation coefficient (ICC) analyses demonstrated substantial agreement among all antibody clones (k=0.639 to 0.791) and excellent reliability among SP263, 22C3, and E1L3N antibodies (ICC, 0.929 to 0.949) in TC staining. Compared with the other 3 clones, SP142 TC staining was lower with only moderate correlation (ICC, 0.500 to 0.619). Generally, the reliability of immune cell staining was lower compared with TC staining (ICC, 0.519 to 0.866). Our results demonstrate good analytic comparability of all 4 antibodies. The results are encouraging and support growing optimism in the pathology and oncology communities concerning strategies in PD-L1 assay use.

SUBMITTER: Hodgson A

PROVIDER: S-EPMC6750743 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PD-L1 Immunohistochemistry Assay Concordance in Urothelial Carcinoma of the Bladder and Hypopharyngeal Squamous Cell Carcinoma.

Hodgson Anjelica A Slodkowska Elzbieta E Jungbluth Achim A Liu Stanley K SK Vesprini Danny D Enepekides Danny D Higgins Kevin K Katabi Nora N Xu Bin B Downes Michelle R MR

The American journal of surgical pathology 20180801 8

Programmed death ligand-1 (PD-L1) immunohistochemistry is used to guide treatment decisions regarding the use of checkpoint immunotherapy in the management of urothelial carcinoma of the bladder and hypopharyngeal (HP) squamous cell carcinoma. With increasing PD-L1 testing options, a need has arisen to assess the analytical comparability of diagnostic assays in order to develop a more sustainable testing strategy. Using tissue microarrays, PD-L1 expression in tumor cells (TCs) and immune cells ( ...[more]

PMID: 29750666

Similar Datasets

Project description:Purpose:The expression of programmed death-ligand 1 (PD-L1) is common in various solid human cancers and it is an important therapeutic target. However, the expression pattern, clinical significance and potential mechanism of PD-L1 in hypopharyngeal squamous cell carcinoma (HSCC) are still lacking. Methods:PD-L1 expression in HSCC tumor tissues and paired adjacent hypopharyngeal mucosal tissues was detected using immunohistochemistry assay, and the clinical significance of PD-L1 in HSCC was characterized. In vitro assays including cell viability assays, migration assays, invasion assays as well as Western blot assays were performed to illuminate the biological functions and underlying molecular mechanisms of PD-L1 in HSCC development. Results:PD-L1 expression was detected in HSCC samples but we found no positive expression in matched normal hypopharyngeal mucosal tissues. The levels of PD-L1 expression were significantly correlated with advanced clinical progression and poor patient survival. Multivariable analysis of Cox model showed that PD-L1 expression was an independent predictor for the prognosis of HSCC patients. Functional experiments showed that the ectopic expression of PD-L1 markedly influenced the proliferation, migration and invasion of FaDu cells in vitro. Mechanistically, investigations demonstrated that PD-L1 could promote the epithelial-mesenchymal transition of FaDu cells. Meanwhile, PD-L1 knockdown inhibited, while PD-L1 overexpression activated the Akt-mTOR signaling pathway in FaDu cells. The EMT induced by PD-L1 overexpression could be reversed by the Akt inhibitor. Conclusion:In summary, the expression of PD-L1 can act as a significant biomarker for the adverse clinicopathological features and poor prognosis of patients with HSCC. PD-L1 can promote the proliferation, migration and invasion of FaDu cells and consequently enhance the aggressiveness. Moreover, PD-L1 induces EMT through AKT-mTOR signaling pathway. These suggest that PD-L1 has important tumor-intrinsic functions independent of its immunopathogenic effects.

Dataset Information

PD-L1 Immunohistochemistry Assay Concordance in Urothelial Carcinoma of the Bladder and Hypopharyngeal Squamous Cell Carcinoma.

Publications

PD-L1 Immunohistochemistry Assay Concordance in Urothelial Carcinoma of the Bladder and Hypopharyngeal Squamous Cell Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets