Immunohistochemical Expression of P15 (INK4B) and SMAD4 in Advanced Gastric Cancer

Abstract

Background: P15 (a cyclin- D- kinase inhibitor) and SMAD4 (a signal transducer of the TGF-β pathway) are two closely related proteins which may have an important role in gastric carcinogenesis. Materials and Methods: Sixty-three gastric carcinomas were studied. P15 and SMAD4 immunohistochemical expression was assessed with the DCS114.1 and BC/B8 mouse monoclonal antibodies, respectively. The results were tested for correlation with several clinicopathological parameters and patient survival. Results: Fifteen out of the 18 (83%) P15-positive tumors also exhibited preserved SMAD4 positivity (p=0.001). Loss of P15 expression was more frequent in the intestinal type of carcinoma (p=0.047). The survival rates were significantly higher for patients with reduced SMAD4 expression, in cases of well- or moderately differentiated tumors (p=0.042). Conclusion: P15 gene silencing might be an important event in the tumorigenesis of gastric adenocarcinomas of the intestinal type. Smad4 may behave as a tumor promoter in low grade tumors. The observed association between P15 and SMAD4 expression supports the inductive role of Smad4 in p15 transcription.