P2.01-028 Prognostic Significance of GLUT1 and CAIX Expression: Correlation with Volume-Based PET Parameters in Non-Small Cell Lung Cancer

Abstract

Glucose transporter type 1 (GLUT1) and carbonic anhydrase IX (CAIX) represent glucose metabolism and tissue hypoxia, respectively. The purpose of this study is to measure the GLUT1 and CAIX expression and volume-based 18F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters in non-small cell lung cancer (NSCLC) patients and examined the correlations between above parameters and their prognostic significance. We evaluated GLUT1 and CAIX expression by immunohistochemical methods and volume-based FDG PET parameters in 269 NSCLC patients treated with surgical resection (158 adenocarcinoma, 93 squamous cell carcinoma and 18 other type carcinoma). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of NSCLC were measured using pretreatment 18F-FDG PET/CT. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of MTV or TLG. Correlations between GLUT1, CAIX, MTV, TLG, and clinicopathological factors were assessed, and prognostic significance was determined. The GLUT1 expression was identified in 99% of squamous cell carcinoma and 50% of adenocarcinoma. In patients with adenocarcinoma, GLUT1 expression showed positive correlation with MTV or TLG (P = 0.012 and P = 0.037, respectively). In patients with squamous cell carcinoma, correlation analyses between GLUT1, MTV and TLG were not performed because most cases of squamous cell carcinoma showed GLUT1 positivity. There was no correlation between CAIX expression, MTV and TLG in squamous cell carcinoma and adenocarcinoma. In cases with adenocarcinoma, GLUT1-positive patients had lower overall survival (OS) rates and lower recur-free survival (RFS) rates than GLUT1-negative patients (P < 0.001 and P = 0.004, respectively). CAIX expression was not significantly associated with either OS or RFS in squamous cell carcinoma and adenocarcinoma. Patients with high MTV or TLG had significantly lower OS rates and lower RFS rates than patients with low MTV or TLG in adenocarcinoma. High GLUT1, TLG and MTV were significantly associated with adverse clinicopathologic variables. When patients with adenocarcinoma were stratified into two groups (High GLUT1 and TLG vs. the other 3 groups), high GLUT1 and TLG was an independent prognostic marker for OS in multivariate analysis (P = 0.003). Our results show that high GLUT1 expression levels were significantly associated with MTV or TLG in patients with adenocarcinoma. High GLUT1 and TLG was an independent prognostic marker for OS. High GLUT1 and TLG can be used to identify a subgroup of patients with adenocarcinoma at high risk of recurrence or progression who may benefit from aggressive chemotherapy or radiotherapy.