Análise imuno-histoquímica de marcadores apoptóticos Bcl-2 e Bax em sarcomas de partes moles de extremidades: um estudo de microarranjos de tecidos

Abstract

Sarcomas are a heterogeneous group of tumors that arise from mesenchymal tissues which represent about 1% of all diagnosed solid malignant tumors in adults. Changes that affect the tumor growth such as the deregulation of apoptosis, through overexpression of the Bcl-2 family proteins, have been associated with the prognosis of patients in various types of cancers, including soft tissue sarcomas (SPM). The Bcl-2 family proteins include anti-apoptotic and proapoptotic proteins such as proteins Bcl-2 and Bax, respectively. Despite the evidence, the prognostic value of these proteins, as well as the association with clinicopathological factors, remain controversial. The objective of this study was to investigate the clinical significance of the expression of apoptosis-related markers Bcl-2 and Bax in 86 patients with STS of extremities by immunohistochemical analysis on a tissue microarray construction. Cytoplasmic expression of Bax and Bcl-2 was detected in 25.9% and 66.7% of the cases, respectively. Overexpression of both Bcl-2 and Bax was directly associated with synovial sarcoma, histological grade and clinical stage. A significant association between Bax and Bcl-2 expression was also observed. The 5-year overall survival (OS) for the group was 57%, being lower for cases with Bcl-2 overexpression (47.6% vs 58.3%) and Bax overexpression (50% vs 66.7%), although such difference was not significant. After multivariate analysis, the histological grade remained as an independent prognostic factor (p=0.043, HR=8.0, 95% CI, 1.1-60.1). Bcl-2 family proteins have been tested as therapeutic targets in some clinical studies in several cancers. In our study, overexpression of both Bcl-2 and Bax was associated with histological grade and clinical stage of the tumors, which are classical factors of poor prognosis. Thus, we suggest the use of these proteins as potential prognostic markers in STS of extremities, providing a more appropriate therapeutic planning for each patient.