유방암 환자에서 Survivin, bcl-2, p53 발현이상 및 세포자멸사에 대한 예후인자로서의 가치

Abstract

Purpose Survivin is a member of the inhibitor of apoptosis (IAP) protein family, and it is involved in the regulation of cell division. The over-expression of survivin has been reported to be associated with the parameters for a poor prognosis in most human cancers, including lung, breast, colon, stomach, esophagus, pancreas, etc. In this study, we examined the expression of a member of a novel IAP protein family, survivin, in breast cancer and its association with tumor cell apoptosis and the overall prognosis.

Methods 80 cases of formalin-fixed paraffin-embedded breast cancer tissue were immunostained with, using polyclonal survivin (Novus Biologicals, Littleton, USA), monoclonal bcl-2 (DAKO, Carpinteria, USA), and monoclonal p53 antibodies (DAKO, Carpinteria, USA). The histochemical method used for the analysis of apoptosis was based on ApopTag® Peroxidase In Situ OligoLigation (ISOL) Apoptosis Detection Kit (CHEMICON International Inc. Temecula, USA).

Results Immunohistochemical analysis showed that cytoplasmic survivin expression was positive in 43 of 80 cases (53.8%) of breast carcinomas and it was positive for 70% of the cases that showed a bcl-2 expression tumors. Statistical analysis revealed that the survivin expression was correlated with lymph node metastasis, the tumor stage, and the histological grade. Although the survivin expression was not correlated with p53 mutations, the survivin positive cases were associated with a bcl-2 expression (p=0.015) and a reduced apoptotic index (p=0.024). On the Cox proportional hazard model analysis, the apoptotic index was not identified as a significant independent predictor of overall survival (p=0.072), although the patients with a low apoptotic index (<0.2%) had a worse survival rates than those patient in the group with a high apoptotic index (≥0.2%).

Conclusion The results suggest that apoptosis inhibition of apoptosis by survivin may be a prognostic parameter for a worse outcome in breast carcinoma patients.