A101: Expression of Glucose Transporter 1 (GLUT1) is a marker for poor prognosis in Oesophageal Adenocarcinoma

Richard C Turkington1,5,Gerald Li2,Leanne Stevenson1,Chintapuza Chisambo3,Damian McManus3,Stephen McQuaid3,Ken Arthur3,Jacqueline James3,Manuel Salto-Tellez3,Darragh McArt2,Peter Hamilton2,Pierre Lao-Sirieix4,Rebecca C Fitzgerald4,Martin Eatock1,5,Richard D Kennedy1

1Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK,2Department of Bioinformatics, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK,3Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK,4Hutchison/MRC Cancer Unit, University of Cambridge, Cambridge, UK,5Northern Ireland Cancer Centre, Belfast City Hospital, Belfast, UK

Presenting date: Monday 2 November
Presenting time: 12.20-13.10

Background

Glucose Transporter 1 (GLUT1) has an important role in tumour metabolism and is upregulated in response to hypoxic stress. We examined GLUT1 expression as a marker of poor prognosis in operable oesophageal adenocarcinoma (OAC). We hypothesized that the presence of a high degree of intra-tumoural hypoxia, as assessed by GLUT1 staining, would identify a poor prognostic OAC sub-group.

Method

156 formalin fixed paraffin-embedded (FFPE) OAC tumour samples were used to construct a Tissue Microarray (TMA). All patients received neo-adjuvant chemotherapy prior to surgical resection at the Belfast Trust between 2004 and 2012. GLUT1 staining was scored by two independent observers based on intensity and percentage of tumour cells staining positive for GLUT-1 antibody (Q score). The Pathology Integromics in Cancer Database (PICan) was used to determine the optimal marker threshold for GLUT1 positivity/negativity.
Validation was performed in a TMA of 431 oesophageal, gastro-oesophageal and gastric adenocarcinomas collected at 5 UK centres between 1994 and 2006.

Results

In the test set 36 patients (24.5%) were scored as negative for GLUT1. GLUT1 negative patients had significantly improved relapse-free (HR 0.53, 95% CI 0.33-0.85; p=0.0086) and overall survival (HR 0.61, 95% CI 0.38-0.99; p=0.046) with a median survival of 43.9 and 30.3 months for GLUT1 negative and positive patients, respectively. The presence of any GLUT1 staining was taken to represent a GLUT1 positive case.
In the validation set 172 patients were GLUT1 negative (39.9%) and had a significantly improved overall survival (HR 0.74, 95% CI 0.58-0.94; p=0.013) with a median survival of 34 and 18 months for GLUT1 negative and positive patients respectively.

Conclusion

This study represents the first analysis of GLUT1 in OAC and the first to validate this marker in an independent dataset. Positive GLUT1 staining identifies a poor prognosis sub-group and is a novel prognostic marker following neo-adjuvant chemotherapy in OAC.