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

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.

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

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.

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.