Intracellular localization of survivin determines biological behavior in colorectal cancer

Abstract

Survivin is a bifunctional protein that suppresses apoptosis and regulates cell division and is highly expressed in various human cancers. Recently, the intracellular localization of survivin in tumors has been suggested as a prognostic marker, but the molecular mechanisms are not understood. The aims of the present study were to investigate the different localization of survivin expression in colorectal carcinoma and expression of survivin relationships with clinicopathological factors and patient survival. Immunohistochemical analyses of 142 cases of advanced colorectal cancer showed that 109 (76.8%) cases expressed survivin in the nucleus and 29 cases (20.4%) in the cytoplasm. Cytoplasmic survivin overexpression was associated with a poor prognosis, but nuclear survivin overexpression was associated with a better prognosis. Subcellular distribution of survivin in five cases of cancerous or surrounding normal tissues derived from fresh biopsy of non-fixed samples of colorectal cancer patients was further demonstrated by Western blotting. Survivin was primarily found in the insoluble fraction. Interestingly, regardless of survivin protein levels in the insoluble fraction, patients who had cancerous tissue expressing cytoplasmic and nuclear soluble survivin suffered from lymph nodes metastases. These data suggest that the function of cytoplasmic survivin might be important for malignant progress and the levels of cytoplasmic and nuclear soluble survivin might be more relevant for prognostic factors for colorectal cancer than the total amount of survivin.