Expression of survivin and its relationship to loss of apoptosis in breastcarcinomas

Aberrant inhibition of programmed cell death (apoptosis) prevents normal ho meostasis and promotes tissue tumorigenesis, but whether it also influences the outcome of common cancers has remained arguable. The expression of a n ovel IAP apoptosis inhibitor, survivin, in breast cancer and its associatio n with tumor cell apoptosis and overall prognosis were examined in this stu dy, Immunohistochemical analysis showed that survivin expression was positi ve in 118 of 167 cases (70.7%) of breast carcinomas of histological stages I to III, In contrast, no expression of survivin in adjacent normal tissue was detected, Although survivin expression was not correlated with p53 muta tions, survivin-positive cases were strongly associated with bcl-2 expressi on (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 a poptotic index (<0.52%) had worse survival rates than the group with high a poptotic index (greater than or equal to 0.52%; P = 0.028), and multivariat e Cox proportional hazard model analysis identified apoptotic index as an i ndependent prognostic factor (P = 0.024). The results suggest that apoptosi s inhibition by survivin, alone or in cooperation with bcl-2, is a signific ant prognostic parameter of worse outcome in breast carcinoma.