Identification of glucose transporter type 1 overexpression as a predictor of survival in patients with malignant pleural mesothelioma

Abstract

7199 Background: Malignant pleural mesothelioma (MPM) is characterized by resistance to cytotoxic therapy dependent in part on apoptosis induction. Apoptosis and glycolysis are linked. The aim of this study was to determine the expression and prognostic significance of glucose transporter 1 (GLUT-1) in MPM. Methods: GLUT-1 was measured in 51 archival MPM specimens by immunohistochemistry. Placenta was used as a positive control with antibody diluent as a negative control. 36 MPM patients (pts) were previously treated in 3 consecutive phase II clinical trials at St Bartholomew's Hospital (vinorelbine1 14 pts, vinorelbine/oxaliplatin 7 pts, irinotecan cisplatin mitomycin C 15 pts). GLUT-1 intensity and extent were scored in duplicate and impact on response rate (RR), progression free survival (PFS) and overall survival (OS) studied. Comparison was made with the EORTC prognostic score (EPS)2. Results: GLUT-1 was expressed in 12 specimens (23%). HIF-1α expression was observed in 79%. No association with between GLUT-1 and RR was observed (χ2 test p > 0.05). Trend to shorter PFS was observed in GLUT-1 positive pts. PFS was 4.4 months (95% confidence limits (CI) 0–11) compared to 6.9 months (95% CI 4.8–9.0, log rank statistic (LR) 0.9, p > 0.05). OS was worse in GLUT-1 positive MPM, 9.4 months (95% CI 4.9–14.8), compared to 14.2 months (95% CI 11.0–17.4, LR 4.2, p = 0.04). The EPS showed a trend to worse survival for poor risk patients with an OS of 12.5 months (95% CI 8.0–17.0) compared to good risk patients with an OS of 14.0 months (95% CI 2.1–25.8, LR 3.3 p = 0.07). High resolution, genome-wide array comparative genomic hybridisation studies are in progress investigating links between DNA copy number changes and glycolytic protein expression and will be presented. Conclusions: GLUT-1 is overexpressed in some pts with MPM and predicts for poor clinical outcome at least as efficiently as the EORTC prognostic score 2. Identification of pts with GLUT-1 positive MPM at diagnosis should facilitate design and interpretation of clinical trials.