Alterations of retinoblastoma protein and p16INK4 protein expression in extrahepatic bile duct carcinomas.

BACKGROUND/AIMS: Human cancer development results from dysfunction of G1-phase regulators of the cell cycle. Retinoblastoma protein and p16INK4 are the most essential links between cell cycle control and cancer. We examined the expression of p16INK4 and pRb and their possible prognostic relevance in 34 extrahepatic bile duct carcinomas.

METHODOLOGY: Expression of pRb and p16INK4 was determined using immunohistochemical techniques. Associations between expression of pRb and p16INK4 and the clinicopathological features were analyzed by using the chi 2 test and survival analysis was performed by Log-rank test.

RESULTS

Two (6%) extrahepatic bile duct carcinomas were pRb negative, 26 (76%) showed pRb overexpression, and 6 (18%) demonstrated moderate expression. Twenty-two (65%) tumors were p16INK4 negative and 12 (35%) were p16INK4-positive. Cases with pRb-negative or pRb overexpression were significantly correlated with tumor progression (P = 0.004) and TNM stage (P = 0.009). Alterations in pRb and p16INK4 expression did not correlate with patient outcome.

CONCLUSIONS

Alterations of pRb and p16INK4 expression are frequently involved in extrahepatic bile duct carcinomas, and that aberrant pRb expression significantly associates with tumor progression.