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Overexpression of Retinoblastoma Protein Predicts Decreased Survival and Correlates with Loss of p16^INK4 Protein in Gallbladder Carcinomas¹

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan

This study was designed to determine whether the level of retinoblastoma protein (pRb) expression predicts tumor progression and prognosis in gallbladder carcinomas (GBCs) and the relationship between pRb and p16^INK4 protein expression. The expression of these two proteins was evaluated immunohistochemically in 37 tumors from 36 patients with GBC. pRb loss and overexpression were observed in 5 (13.5%) and 18 (48.6%) of the 37 tumors, respectively. Both pRb loss and overexpression were significantly correlated with advanced TNM stage, lymph node metastasis, and tumor perineural invasion. Moreover, pRb overexpression was significantly associated with decreased overall survival (P = 0.001; log-rank test). Further analysis indicated that the influence of pRb overexpression on survival was independent of TNM stage and lymph node metastasis. Loss of p16^INK4 protein was observed in 28 of the 37 GBCs (75.7%), but was not significantly associated with any clinicopathological factors or survival. pRb overexpression was significantly associated with the loss of p16^INK4 protein (P < 0.0001). These results suggest that pRb overexpression significantly predicts decreased survival in GBCs.

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