Expression And Clinical Significance Of Survivin, And Its Correlation With Expression Of P53, Bcl-2 And Bax In Gastric Carcinoma

Objective:To study the expression of apoptosis inhibitor protein of Survivin in gastric carcinoma and its correlation with clinicopathologic parameters and prognosis. To examine the relationship between the Survivin expression and the expression of p53, Bcl-2 and Bax in gastric carcinoma.Methods: Immunohistochemical staining of Survivin, p53 , Bcl-2 and Bax were performed by the standard streptavidin-peroxidase (SP) technique for the paraffin-embeded sections of 105 gastric cancers. The relationship between expression of Survivin with the clinicopathologic parameters, prognosis and the expression of p53, Bcl-2 and Bax was analyzed, respectively. Kaplan-Meier method and Cox proportional hazards model analysis were used to investigate the correlation between Survivin expression and survival rate of the patients for whom long term follow up data were available.Results: 1. The expression of Survivin protein in gastric carcinomaSurvivin was expressed 50 of 105 cases of human gastric carcinoma. Expression of Survivin was observed in the cytoplasm of adenoma with gastric carcinoma cells. In contrast, no immunoreactivity of Survivin was seen in neighboring normal tissues and tissues adjacent to the tumor. 2.Relationship between expression of Survivin with the clinicopathologic parameters of gastric carcinomaThe positive expression of Survivin was significantly related to the infiltration ,lymph node metastasis and TNM staging(r=0.283, 0.230 and 0.234,respectively, P<0.05), but had no relation with the elements of age, sex, tumor location, Borrmann's classification and histological differentiation(P>0.05).3. Correlation between Survivin expression and patient survival in gastric carcinomaThe1, 3, 5-year survival rate after operation was significantly lower in patients with Survivin positively staining than that of patients with Survivin negative (52.0%, 36.0%, 30.0% vs 81.8%, 63.6%, 56.4%, P<0.05, log-rank test). Multivariate Cox proportional hazards model analysis identified Survivin expression as an independent prognostic indicator of disease-free survival (P = 0.004, relative risk = 0.516).4. Correlation between Survivin expression and the expression of p53 , Bcl-2 and Bax in gastric carcinomaThe expression of Survivin significantly segregated with p53- and Bcl-2-positive cases [52.0 % vs 30.9% (P< 0.05) and 58.0% vs 36.4% (P< 0.05), respectively] and with a decreased Bax expression as compared with that of Survivin-negative tumors (26.0% vs 45.5%, P< 0.05).Conclusions:1.Survivin protein was highly overexpressed in gastric carcinoma. Its expression was associated with unfavorable clinicopathological parameters infiltration , lymph node metastasis and TNM staging and represents an independent marker for prognosis of gastric carcinoma. 2.Up-regulation of Survivin and Bcl-2, de-activation of antioncoprotein p53 and low Bax expression might play synergetic roles in the process of carcinogenesis of gastric carcinoma.