Squamous differentiation is a potential biomarker predicting tumor progression in patients treated with pembrolizumab for urothelial carcinoma

This study aims to clarify the predictors of disease progression for ICI treatment in patients with urothelial carcinoma. We analyzed the response pattern of 23 urothelial carcinomas treated with pembrolizumab and its association with pathological features and potential immunohistochemical markers including EGFR, MDM2, p53, p16, and programmed cell death ligand-1 (PD-L1) expression and CD8- and CD204-positive cell infiltration. During ICI therapy, 13 (57 %) patients showed progressive disease including 6 (26 %) with hyperprogressive disease. Notably, squamous differentiation combined with MAC387 expression was observed exclusively in cases with progressive disease (6 of 13, 46 %); it was not present in cases with stable disease or partial/complete response (0 of 10, p = 0.0019). All tumors with squamous differentiation showed positive staining for EGFR. Additionally, the loss of p16 expression occurred more frequently in cases with progressive disease (8 of 13, 62 %) than in other cases (3 of 10, 30 %), but this finding did not reach statistical significance. Squamous differentiation was also significantly associated with shorter overall survival. Based on our observations, squamous differentiation may be a novel biomarker for predicting disease progression in patients with urothelial carcinoma who receive pembrolizumab.PMID:33610951 | DOI:10.1016/j.prp.2021.153364
Source: Pathology, Research and Practice - Category: Pathology Authors: Source Type: research