title: BH3-only protein Bim predicts advanced stage of cutaneous melanoma.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Skin Cancer Center of the Department of Dermatology, Ruhr-University Bochum, Bochum, Germany. t.gambichler@klinikum-bochum.de.
authors.forename: T
authors.initials: T
authors.lastname: Gambichler
authors.affiliation: Skin Cancer Center of the Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Rooms
authors.affiliation: Skin Cancer Center of the Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Scholl
authors.affiliation: Skin Cancer Center of the Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Stockfleth
authors.affiliation: Skin Cancer Center of the Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stücker
authors.affiliation: Skin Cancer Center of the Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sand
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D000072224:Bcl-2-Like Protein 11