BH3‐only protein Bim predicts advanced stage of cutaneous melanoma. (29th June 2016) - Gambichler, T.
Abstract: Background: Bim having strong pro‐apoptotic effects belongs to the BH3‐only proteins of the Bcl‐2 protein family and contributes to survival pathways in cancer cells. Objectives: We aimed to investigate Bim protein expression in cutaneous melanoma (CM). Methods: Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. Results: The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly ( P < 0.0001) higher than that observed in metastases (2.8 ± 1.1). Low Bim expression was significantly associated with primary nodular melanoma type ( P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness ( r = −0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = −0.60; P < 0.0001), disease relapse ( r = −0.18; P = 0.034) and disease‐related death ( r = −0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression ( P = 0.0010, odds ratio: 0.22, 95% CI: 0.10–0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse ( P = 0.40) and disease‐related death ( P = 0.77). Conclusions: Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro‐apoptotic BH3‐only protein might be a potent biomarker and promising therapeutic target.