Expression of survivin and its relationship to loss of apoptosis in breast carcinomas.

Aberrant inhibition of programmed cell death (apoptosis) prevents normal homeostasis and promotes tissue tumorigenesis, but whether it also influences the outcome of common cancers has remained arguable. The expression of a novel IAP apoptosis inhibitor, survivin, in breast cancer and its association with tumor cell apoptosis and overall prognosis were examined in this study. Immunohistochemical analysis showed that survivin expression was positive in 118 of 167 cases (70.7%) of breast carcinomas of histological stages I to IH. In contrast, no expression of survivin in adjacent normal tissue was detected. Although survivin expression was not correlated with p53 mutations, survivin-positive cases were strongly associated with bcl-2 expression (78.0% versus 47.5%; P = 0.0005) and reduced apoptotic index (0.62% +/- 0.51% versus 1.27% +/- 1.37%; P < 0.0001). In addition, patients with low apoptotic index (<0.52%) had worse survival rates than the group with high apoptotic index (> or =0.52%; P = 0.028), and multivariate Cox proportional hazard model analysis identified apoptotic index as an independent prognostic factor (P = 0.024). The results suggest that apoptosis inhibition by survivin, alone or in cooperation with bcl-2, is a significant prognostic parameter of worse outcome in breast carcinoma.