Clinical Significance Of P53,p16,bcl-2 And Bax Expression In Gastric Carcinoma

Clinical Significance ofp53,p16, bcl-2 and bax Expression in Gastric CarcinomaZHEJIANG UNIVERSITY MEDICAL COLLEGE SURGERYPostgraduate Ma Yu Advisor Prof. Cao Lipin, MDObjective: Gastric cancer continues to be a highly aggressive malignancy with poor prognosis and low survival rates. The survival of patients with gastric cancer depends mainly on the stage of the disease, with early gastric cancer having a 5-year survival of 90-100% and advanced tumors a 5-year survival of 15-20%. The role of other prognostic factors in these tumors is still under investigation The aim of this study was to investigate the clinical significance of p53, p!6, bcl-2 and bax expression in gastric carcinoma with special reference to the prognosis.Methods: One hundred and fifty-two gastric carcinomas undergoing operation in Shengzhou People's hospital, Shengzhou City. Zhejiang Porvince between 1991 and 1998 were evaluated for expression of the oncogenes p53. p!6, bcl-2 and bax in formalin-fixed and paraffin-embedded tumor tissue utilizing Avidin-Biotm immunohisto-chemistry techniques. Statistical correlations with stage, histoiogictype. differentiation degree, location, size, and overall survival were done. The Cox proportional hazard model was also performed to evaluate which factors had an independent prognostic value.Results: Of 152 resected gastric cancers. 110 (72.4%) were p16 positive, 41 (27%) were bcl-2 positive, 126 (82.9%) were bax positive and 49(32.2%) showed p53 overexpression. Differences were observed in the frequency of p]6 positivity with respect to age. gender, tumor size, and differentiation degree. The frequency of p53 positivity cells in weii-differentiated tumors was significantly higher than that in poorly differentiated tumors (41 .9% vs. 25.6%; P = 0.034). The frequency of bax positivity in tumors with T1-T2 was significantly higher than that in tumors with T3-T4 (73.8% vs. 26.2%; P = 0.016). Neither depth of tumor invasion nor histological differentiation had a positive correlation with bci-2 overexpression. In patients with bcl-2 (-) and bax (+). survival was significantly longer in those with p53-negative tumors (P = 0.0329). In a multivanate analysis, the depth of tumor infiltration, differentiation degree, size, the presence of nodal metastases. perioperation blood transfusion and the expression of p!6 were independent prognostic factors in gastric cancer.Conclusions: The results of the current study suggest that p53 overexpression is a relatively early event while aberrant p!6 or bax expression is a relatively later event in gastric carcinogenesis. The data also imply that expression of p!6 may be a useful prognostic factor for patients with gastric carcinoma, but the expression of p53. bcl-2 or bax as detected by immunohistochemistry were of no value in predicting the prognosis of patients with gastric carcinoma independently whereas co-examination of p53 expression in bax negative and bcl-2 positive tumors might be useful for estimating the prognosis of patients with gastric cancer.