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.

Combined assessment of peritumoral Th1/Th2 polarization and peripheral immunity as a new biomarker in the prediction of BCG response in patients with high-risk NMIBC

“…In addition, the expression of PD-L1 could be slightly lower than the expression reported in other studies, as differences in the percentage of positive cells have been described for different anti PD-L1 antibody clones. 42 In conclusion, the BCG response in high-risk NMIBC patients is associated with local and systemic immune alterations in the bladder tissue prior to BCG treatment. Our results suggest the potential predictive value of the combined assessment of peritumoral Th1/Th2 polarization and peripheral immunity composition for the identification of individuals who will obtain more benefit from BCG treatment.…”

Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

“…Two recent studies investigated the concordance of different PD‐L1 assays in urothelial cancer tissue microarrays, and found PD‐L1 expression in 12–29% of samples . Tretiakova et al .…”

“…9,10 Two recent studies investigated the concordance of different PD-L1 assays in urothelial cancer tissue microarrays, and found PD-L1 expression in 12-29% of samples. 11,12 Tretiakova et al found concordant PD-L1 assay outcome in matched primary urothelial carcinoma and lymph node metastasis in 90%. 12 This number is slightly higher than the rate of 77-82% in our series, and can be explained by the fact that they used PD-L1 assays taking tumour cell expression into account, while the SP142 scoring algorithm is based on immune cell expression only.…”

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

“…Expression of PD-L1 in cancer cells results in anergy of T lymphocytes (by targeting PD-1 on their surface); this way, tumor cells escape destruction by the immune system and maintain a subverted immune-suppressive tumor microenvironment [27,28]. It has become routine, then, for pathology departments to assess PD-L1 expression by immunohistochemistry in BlCa tissue specimens [29,30].…”