EXPRESSION OF A NOVEL ANTIAPOPTOSIS GENE, SURVIVIN, CORRELATED WITH TUMOR-CELL APOPTOSIS AND P53 ACCUMULATION IN GASTRIC CARCINOMAS

A novel inhibitor of apoptosis designated survivin has recently been f ound in many common human cancers but not in normal tissues. A potenti al distribution of survivin in gastric cancer and its implication for apoptosis inhibition have been investigated. Recombinant survivin expr essed in Escherichia coli as a glutathione S-transferase fusion protei n was used to raise a novel panel of mouse monoclonal antibodies. In a n immunohistochemical analysis of 174 cases of gastric carcinomas (sta ges I-III), anti-survivin monoclonal antibody 8E2 (TgG1) reacted with 34.5% of cases (60 of 174 cases) with a variable number of tumor cells stained (20-100%). In contrast, no expression of survivin in neighbor ing normal tissues was observed. When stratified for p53 and bcl-2 exp ression and apoptotic index, the expression of survivin significantly segregated with p53- and bcl-2-positive cases [56.1 versus 15.2% (P = 0.001) and 69.2 versus 31.6% (P = 0.006), respectively] and with a dec reased apoptotic index as compared with that of survivin-negative tumo rs (0.97 +/- 0.64 versus 0.62 + 0.39%, P < 0.001). These data identify a role for survivin in promoting aberrantly increased cell viability in gastric cancer and suggest a potential correlation between accumula ted p53 and survivin expression in neoplasia.