Glucose transporter 1 expression as a marker of prognosis in oesophageal adenocarcinoma

Abstract

Background: The current TNM staging system for oesophageal adenocarcinoma (OAC) has limited ability to stratify patients and inform clinical management following neo-adjuvant chemotherapy and surgery. Results: Functional genomic analysis of the gene expression data using Gene Set Enrichment Analysis (GSEA) identified GLUT1 as putative prognostic marker in OAC. In the discovery cohort GLUT1 positivity was observed in 114 patients (80.9%) and was associated with poor overall survival (HR 2.08, 95% CI 1.1-3.94; p=0.024) following multivariate analysis. A prognostic model incorporating GLUT1, CRM and nodal status stratified patients into good, intermediate and poor prognosis groups (p < 0.001) with a median overall survival of 16.6 months in the poorest group. In the validation set 182 patients (69.5%) were GLUT1 positive and the prognostic model separated patients treated with neo-adjuvant chemotherapy and surgery (p < 0.001) and surgery alone (p < 0 .001) into three prognostic groups. Patients and Methods: Transcriptional profiling of 60 formalin fixed paraffinembedded (FFPE) biopsies was performed. GLUT1 immunohistochemical staining was assessed in a discovery cohort of 141 FFPE OAC samples treated with neo-adjuvant chemotherapy and surgery at the Northern Ireland Cancer Centre from 2004-2012. Validation was performed in 262 oesophageal adenocarcinomas collected at four OCCAMS consortium centres. The relationship between GLUT1 staining, T stage, N stage, lymphovascular invasion and circumferential resection margin (CRM) status was assessed and a prognostic model developed using Cox Proportional Hazards. Conclusions: GLUT1 staining combined with CRM and nodal status identifies a poor prognosis sub-group of OAC patients and is a novel prognostic marker following potentially curative surgical resection.