Immunohistochemically Detectable Bcl-2 Expression in Metastatic Melanoma: Association with Survival and Treatment Response

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Abstract
Objective: The antiapoptotic protein Bcl-2 is supposed to influence the treatment responsiveness of different malignancies. In the present study the prognostic and predictive significance of Bcl-2 expression for survival and response to an administered therapy was explored in patients with metastatic melanoma. Also, the correlation between Bcl-2 expression and proliferation activity of tumor cells was defined to examine the regulatory role of Bcl-2 in proliferation. Materials and Methods: Sixty metastatic melanomas obtained from patients treated with chemoimmunotherapy were examined by immunohistochemistry with anti-Bcl-2 and anti-Ki-67 (MIB-1) antibodies. Proliferation activity was expressed in percentages as MIB-1 index. Results: The presence of Bcl-2 immunoreactivity was associated with a significantly lower MIB-1 index (p = 0.016), and a longer disease-free survival (p = 0.004). The lack of Bcl-2 expression was related to a higher response rate to therapy in comparison to a diffuse and focal pattern of Bcl-2 expression (p = 0.017). Although the presence of Bcl-2 immunoreactivity as such did not correlate with survival after the initiation of chemoimmunotherapy, the focal Bcl-2 expression pattern was strongly associated with a worse prognosis compared to a diffuse expression or a lack of Bcl-2 staining (p < 0.0001). Conclusions: Our results support the role of Bcl-2 in the regulation of cell proliferation and suggest that an increase of metastatic potential and progression of malignant melanoma is associated with a loss of Bcl-2 expression. The lack of Bcl-2 expression could be a predictor of the response to chemoimmunotherapy, whereas the Bcl-2 expression pattern, possibly indicating the heterogeneity of the tumors, might be a potential prognostic factor for survival after the initiation of therapy.