INHIBITION OF APOPTOSIS BY SURVIVIN PREDICTS SHORTER SURVIVAL RATES IN COLORECTAL-CANCER

Deregulated inhibition of apoptosis (programmed cell death) may facili tate the insurgence of neoplasia, but whether it also influences the o utcome of common cancers has remained controversial. In this study, we investigated the expression of a novel inhibitor of apoptosis, surviv in, in colorectal cancer and its relationship with tumor cell apoptosi s and overall prognosis. By immunohistochemistry, survivin was express ed in 91 of 171 (53.2%) cases of colorectal carcinomas of histological stages 0 to IV. In contrast, normal colon epithelium did not express survivin. Although survivin expression did not correlate with p53 abno rmalities (46.5% versus 58.0%; P = 0.18), survivin-positive cases were strongly associated with bcl-2 expression (72.5% versus 27.4%; P < 0. 0001) and reduced apoptotic index (0.76% +/- 0.39% versus 1.17% +/- 0. 62%; P < 0.0001), Expression of survivin alone in bcl-2-negative (disc ordant) cases also resulted in reduced apoptotic index (0.82% +/- 0.57 % versus 1.16% +/- 0.66%; P = 0.0046), When analyzed for prognostic si gnificance, patients with low apoptotic index (<0.97%) had worse survi val rates than the group with high apoptosis (P < 0.001), and a multiv ariate Cox proportional hazard model identified reduced apoptosis as a n independent predictive factor for overall survival (P < 0.0001), The se data demonstrate that apoptosis inhibition by survivin, alone or in cooperation with bcl-2, is an important predictive/prognostic paramet er of poor outcome in colorectal carcinoma and identify survivin as a new diagnostic/therapeutic target in cancer.