Primary adenocarcinoma of the bladder lacks mismatch repair deficiency and demonstrates PD-L1 expression in tumor-infiltrating immune cells, with implications in both diagnosis and therapeutics

Abstract

Primary adenocarcinoma of the bladder is a rare and highly aggressive disease with no standard therapy. Effectiveness of immune checkpoint blockade in bladder adenocarcinoma is unknown due to lack of clinical trials. Due to the disease rarity, the rate of PD-L1 expression and DNA mismatch repair deficiency is largely unknown. In this study, we examined PD-L1 expression in 56 cases of bladder adenocarcinoma and mismatch repair protein expression in 42 cases of bladder adenocarcinoma using immunohistochemistry. Mismatch repair protein expression was uniformly intact in all cases of bladder adenocarcinoma, in comparison with 19% of advanced colorectal adenocarcinoma being mismatch repair deficient. This finding indicates that mismatch repair proteins may be combined with β-catenin and GATA-3 to create an immunostaining panel which, in addition to clinical studies, can aid in distinguishing bladder adenocarcinoma from secondary involvement by colorectal carcinoma. 4% of cases were found to overexpress PD-L1 in tumor cells while approximately a third of cases were found to display PD-L1 expression in tumor-infiltrating immune cells. These results indicate hypermutators are likely rare in bladder adenocarcinoma, yet 20-30% of the patients may be eligible for immune checkpoint blockade therapy.

Keywords: Bladder adenocarcinoma; Checkpoint inhibitor; Colorectal adenocarcinoma; Immunohistochemistry; Immunotherapy; Mismatch repair; PD-L1.