title: Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmö Diet and Cancer Study.
abstract: BACKGROUND
  We have previously reported that expression of the RNA- and DNA-binding protein RBM3 is associated with a good prognosis in breast cancer and ovarian cancer. In this study, the prognostic value of immunohistochemical RBM3 expression was assessed in incident cases of malignant melanoma from a prospective population-based cohort study.
  
  
  METHODS
  Until Dec 31st 2008, 264 incident cases of primary invasive melanoma had been registered in the Malmö Diet and Cancer Study. Histopathological and clinical information was obtained for available cases and tissue microarrays (TMAs) constructed from 226 (85.6%) suitable paraffin-embedded tumours and 31 metastases. RBM3 expression was analysed by immunohistochemistry on the TMAs and a subset of full-face sections. Chi-square and Mann-Whitney U tests were used for comparison of RBM3 expression and relevant clinicopathological characteristics. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the relationship between RBM3 and recurrence free survival (RFS) and overall survival (OS).
  
  
  RESULTS
  RBM3 could be assessed in 215/226 (95.1%) of primary tumours and all metastases. Longitudinal analysis revealed that 16/31 (51.6%) of metastases lacked RBM3 expression, in contrast to the primary tumours in which RBM3 was absent in 3/215 (1.4%) cases and strongly expressed in 120/215 (55.8%) cases. Strong nuclear RBM3 expression in the primary tumour was significantly associated with favourable clinicopathological parameters; i.e. non-ulcerated tumours, lower depth of invasion, lower Clark level, less advanced clinical stage, low mitotic activity and non-nodular histological type, and a prolonged RFS (RR = 0.50; 95% CI = 0.27-0.91) and OS (RR = 0.36, 95%CI = 0.20-0.64). Multivariate analysis demonstrated that the beneficial prognostic value of RBM3 remained significant for OS (RR = 0.33; 95%CI = 0.18-0.61).
  
  
  CONCLUSIONS
  In line with previous in vitro data, we here show that RBM3 is down-regulated in metastatic melanoma and high nuclear RBM3 expression in the primary tumour is an independent marker of a prolonged OS. The potential utility of RBM3 in treatment stratification of patients with melanoma should be pursued in future studies.
authors.affiliation: Department of Clinical Sciences, Pathology, Lund University, Skåne University Hospital, 221 85 Lund, Sweden.
authors.forename: Liv
authors.initials: L
authors.lastname: Jonsson
authors.forename: Julia
authors.initials: J
authors.lastname: Bergman
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004032:Diet; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D013548:Sweden
chemical_list: C099506:RBM3 protein, human; D016601:RNA-Binding Proteins