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Expression of A Novel Antiapoptosis Gene, Survivin, Correlated with Tumor Cell Apoptosis and p53 Accumulation in Gastric Carcinomas¹

Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka 569-8686, Japan [C-D. L., N. T.], and Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536 [D. C. A.]

A novel inhibitor of apoptosis designated survivin has recently been found in many common human cancers but not in normal tissues. A potential distribution of survivin in gastric cancer and its implication for apoptosis inhibition have been investigated. Recombinant survivin expressed in Escherichia coli as a glutathione S-transferase fusion protein was used to raise a novel panel of mouse monoclonal antibodies. In an immunohistochemical analysis of 174 cases of gastric carcinomas (stages I–III), anti-survivin monoclonal antibody 8E2 (IgG1) 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 neighboring normal tissues was observed. When stratified for p53 and bcl-2 expression 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 decreased apoptotic index as compared with that of survivin-negative tumors (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 accumulated p53 and survivin expression in neoplasia.

¹ Supported in part by a Grant-in-Aid for Scientific Research on Priority Areas-Cancer from the Ministry of Education, Science, Sports and Culture, Japan and by NIH Grants HL43773 and HL54131. This work was done in part during the tenure of an American Heart Association Established Investigatorship Award to D. C. A.

² C-D. L. is a visiting scholar from Zhejiang Medical University, Hangzhou, China.

³ To whom requests for reprints should be addressed, at Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-Machi, Takatsuki City, Osaka 569-8686, Japan. Phone: 81-726-84-6541; Fax: 81-726-84-6541; E-mail: sur001@poh.osaka-med.ac.jp.

Received 2/23/98. Accepted 3/17/98.

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