Overexpression of retinoblastoma protein predicts decreased survival and correlates with loss of p16(INK4) protein in gallbladder carcinomas

This study was designed to determine whether the level of retinoblastoma pr otein (pRb) expression predicts tumor progression and prognosis in gallblad der carcinomas (GBCs) and the relationship between pRb and p16(INK4) protei n expression. The expression of these two proteins was evaluated immunohist ochemically in 37 tumors from 36 patients with GBC. pRb loss and overexpres sion were observed in 5 (13.5%) and 18 (48.6%) of the 37 tumors, respective ly. Both pRb loss and overexpression were significantly correlated with adv anced TNM stage, lymph node metastasis, and tumor perineural invasion. More over, pRb overexpression was significantly associated with decreased overal l survival (P = 0.001; log-rank test), Further analysis indicated that the influence of pRb overexpression on survival was independent of TNM stage an d lymph node metastasis, Loss of p16(INK4) protein was observed in 28 of th e 37 GBCs (75.7%), but was not significantly associated with any clinicopat hological factors or survival, pRb overexpression was significantly associa ted,vith the loss of p16(INK4) protein (P < 0,0001), These results suggest that pRb overexpression significantly predicts decreased survival in GBCs.