PBRM1 Immunohistochemical Expression Profile Correlates with Histomorphological Features and Endothelial Expression of Tumor Vasculature for Clear Cell Renal Cell Carcinoma

SIMPLE SUMMARY: The PBRM1 protein, whose gene is the most frequently mutated one in clear cell renal cell carcinoma (ccRCC) following von Hippel-Lindau, has been proposed as a potential biomarker for ccRCC. However, the association of the PBRM1 immunohistochemical expression with histomorphological features of ccRCC and the endothelial expression of tumor vasculature, which is an important role of the tumor microenvironment related to treatment response, is little known. Recently, our research team has established a vascularity-based architectural classification of ccRCC correlated with angiogenesis and immune gene expression signatures, which could provide prognostic information and function as a surrogate for treatment selection. In the present study, we found the PBRM1 expression was correlated with the architectural patterns. Furthermore, we demonstrated that endothelial expression tended to be lost in cases with low PBRM1 expression. This correlation implied the orchestrated expression of PBRM1, raising the possibility that the cancer cells and their microenvironment interact in ccRCC. ABSTRACT: Loss of the polybromo-1 (PBRM1) protein has been expected as a possible biomarker for clear cell renal cell carcinoma (ccRCC). There is little knowledge about how PBRM1 immunohistochemical expression correlates with the histomorphological features of ccRCC and the endothelial expression of tumor vasculature. The present study evaluates the association of architectural patterns with the PBRM1 expression of cancer cells using a cohort of 425 patients with nonmetastatic ccRCC. Furthermore, we separately assessed the PBRM1 expression of the endothelial cells and evaluated the correlation between the expression of cancer cells and endothelial cells. PBRM1 loss in cancer cells was observed in 148 (34.8%) patients. In the correlation analysis between architectural patterns and PBRM1 expression, macrocyst/microcystic, tubular/acinar, and compact/small nested were positively correlated with PBRM1 expression, whereas alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary, solid sheets, and sarcomatoid/rhabdoid were negatively correlated with PBRM1 expression. PBRM1 expression in vascular endothelial cells correlated with the expression of cancer cells (correlation coefficient = 0.834, p < 0.001). PBRM1 loss in both cancer and endothelial cells was associated with a lower recurrence-free survival rate (p < 0.001). Our PBRM1 expression profile indicated that PBRM1 expression in both cancer and endothelial cells may be regulated in an orchestrated manner.