Disruption of pRb-p16INK4 pathway: a common event in ampullary carcinogenesis.

BACKGROUND/AIMS: Aberrations of the pRb (Retinoblastoma gene protein)-p16INK4 pathway play a critical role in carcinogenesis. Our objective is to evaluate its role in tumorigenesis and the development of ampullary cancer.

METHODOLOGY: We examined expression status of p16INK4 protein and pRb immunohistochemically and assessed their possible prognostic relevance in 36 ampullary cancers.

RESULTS

Thirty-four specimens (94.4%) exhibited alteration of p16INK4 and/or pRb expression, with 63.9% (23/36) of cancers showing p16INK4 negative expression and 94.4% (34/36) pRb abnormal expression. p16INK4 protein negative expression correlated significantly with tumor progression features such as advanced tumor stages (p=0.0291), lymph node metastasis (p=0.005), pancreas invasion (p=0.0002) and duodenum invasion (p=0.0101). Cases with both p16RNK4 protein negative expression and pRb overexpression showed poorer differentiation, more invasive growth (p=0.0425), higher level tumor stages (p=0.0079) and more frequent pancreas invasion (p=0.0024), compared with the others. p16INK4 protein expression showed no relationship with pRb expression (p=0.2199). No association was found in pRb expression status compared with any clinicopathological parameters analyzed.

CONCLUSIONS

The disruption of the pRb-p16NK4 pathway plays an important role in ampullary carcinogenesis, the absence of p16INK4 protein expression might be involved in ampullary tumor progression.