title: High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death.
abstract: BACKGROUND
  High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma.
  
  
  METHODS
  Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett's esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS).
  
  
  RESULTS
  RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS).
  
  
  CONCLUSIONS
  High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation.
authors: Department of Clinical Sciences, Division of Oncology-Pathology, Lund University, Skåne University Hospital, Lund 221 85, Sweden.
authors: Liv
authors: L
authors: Jonsson
authors: Department of Clinical Sciences, Division of Oncology-Pathology, Lund University, Skåne University Hospital, Lund 221 85, Sweden.
authors: Charlotta
authors: C
authors: Hedner
authors: Department of Clinical Sciences, Division of Oncology-Pathology, Lund University, Skåne University Hospital, Lund 221 85, Sweden.
authors: Alexander
authors: A
authors: Gaber
authors: Department of Clinical Sciences, Division of Oncology-Pathology, Lund University, Skåne University Hospital, Lund 221 85, Sweden.
authors: Dejan
authors: D
authors: Korkocic
authors: Department of Clinical Sciences, Division of Oncology-Pathology, Lund University, Skåne University Hospital, Lund 221 85, Sweden.
authors: Björn
authors: B
authors: Nodin
authors: Science for Life Laboratory, AlbaNova University Center, Royal Institute of Technology, Stockholm 106 91, Sweden ; School of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm 106 91, Sweden.
authors: Mathias
authors: M
authors: Uhlén
authors: Department of Clinical Sciences, Division of Oncology-Pathology, Lund University, Skåne University Hospital, Lund 221 85, Sweden.
authors: Jakob
authors: J
authors: Eberhard
authors: Department of Clinical Sciences, Division of Oncology-Pathology, Lund University, Skåne University Hospital, Lund 221 85, Sweden.
authors: Karin
authors: K
authors: Jirström
keywords: Esophageal and gastric adenocarcinoma; Intestinal metaplasia; Prognosis; RBM3 expression