The prognostic value of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue markers in localized renal cell carcinoma: A retrospective study of tissue microarrays using immunohistochemistry

OBJECTIVE:To assess the prognostic roles of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue biomarkers in localized renal cell carcinoma (RCC). METHODS:Patients who underwent a nephrectomy during 1992-2015 and had a primary specimen of their kidney tumor were included. The nine tissue biomarkers were immunohistochemically stained on tissue microarrays of RCC, and the semi-quantitative H-score, including intensity score, was used to grade the sample. The Cox proportional hazards model was used to evaluate tissue markers significant for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after adjusting for significant clinicopathological parameters. RESULTS:Samples from 351 RCC patients were included. The mean age of the patients was 53.9 years; the rates of pathologic T1-2/≥T3 stage, Fuhrman 1+2/3+4 grade, recurrence, and death were 269/65(80.5/19.5%), 222/107 (67.5/32.5%), 6.6%, and 10.5%, respectively. Median OS, CSS, and RFS were 220.6, 220.6, and 147.1 months, respectively. The multivariable analysis showed that pathologic T stage and Fuhrman nuclear grade were significantly associated with OS and CSS. Pathologic T stage and tumor size were associated with RFS. After adjusting for these significant prognostic clinicopathological factors, Ki-67 was significantly associated with OS (hazard ratio [HR], 2.7), CSS (HR, 3.82), and RFS (HR, 4.85) and pS6 was associated with CSS (HR, 8.63) and RFS (HR, 8.51) in the multivariable model (p<0.05). CONCLUSION:pS6 and Ki-67 are significant prognostic factors of RCC; however, BAP1, PBRM1, TGase 2, PD-L1, CA9, PTEN loss, and PSMA markers did not show this association.