Cellular localisation of Survivin: impact on the prognosis in colorectal cancer

Abstract

The present study was designed to determine whether the nuclear or cytoplasmic expression of survivin, was related to clinicopathological parameters and survival in sporadic colon carcinomas. Western blotting of cell fractions and immunocytochemical methodology were used in five human colon cancer cell lines. Immunohistochemical study was performed in formalin-fixed paraffin-embedded section from 46 patients with sporadic colorectal adenocarcinomas with a polyclonal antibody directed against survivin. Apoptotic index was evaluated by using the M30 antibody. Survival rates were estimated by the Kaplan-Meier method and compared using the log-rank test. Multivariate survival analysis was performed by the Cox proportional hazards model. Western blotting and immunocytochemistry analyses confirmed that survivin could be detected both in the nucleus and the cytoplasm. Immunohistochemical analysis demonstrated that 39% of tumours expressed survivin in the nucleus and 41% in the cytoplasm. No relationship was observed between survivin expression and clinicopathological features. Unexpectedly, the apoptotic index appeared to be linked with high survivin nuclear expression. Overall, 3-year observed survival rate was 73% in patients with cytoplasmic survivin expression versus 48% for negative expression (P = 0.14). Survival was 72% versus 50% for positive nuclear survivin expression versus negative (P = 0.16). After adjustment for age and stage, cytoplasmic survivin expression was a significant prognostic factor. A high level of expression was associated to a better survival: RR = 0.35 [0.13-0.98], P = 0.045. These results indicate that the analysis of the subcellular expression of survivin is a determining factor to define the prognostic value. Its evaluation, using a polyclonal antibody, might help clinicians in the stratification of patients with colorectal cancer.