Prognostic Significance of Apoptosis-related Markers in Patients With Soft-Tissue Sarcomas of Extremities.

Abstract

Bcl-2 and Bax proteins are key regulators of apoptosis, a process that is deregulated in many human diseases, particularly cancer. Overexpression of antiapoptotic Bcl-2 protein is associated with drug resistance and poor clinical outcome in cancer patients, whereas the expression of proapoptotic Bax protein, commonly detected in soft-tissue sarcoma (STS), is often associated with chemiosensitivity in different tumors. Studies on the clinical implications of apoptosis-related markers Bcl-2 and Bax in STS are limited. In this study, immunohistochemistry for Bcl-2 and Bax was performed on tissue microarrays of 86 multiple types of adult STS of the extremities. Bcl-2 and Bax positive expression was detected in 25.9% and 66.7% of the sarcomas, respectively. Overexpression of both, Bcl-2 and Bax, was directly associated with histologic grade and clinical stage. A significant association between Bax and Bcl-2 expression was also observed (P=0.007). The 5-year overall survival for the group was 57%, and it was lower for cases that overexpressed Bcl-2 (47.6% vs. 58.3%) and Bax (50% vs. 66.7%), although not statistically significant. After multivariate analysis, only the high histologic grade appeared as an independent prognostic factor for the patients (P=0.043; HR=8.0; 95% CI, 1.1-60.1). In our study, Bcl-2 and Bax expression was significantly associated with histologic grade and clinical stage, which are classic factors of poor prognosis. We suggest the use of these proteins as potential prognostic markers in STS of extremities.