Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma.

Abstract

The overexpression of glucose transporters, especially of Glut-1, is a common characteristic of human malignancies, including head and neck carcinoma. Recently, the assessment of glucose metabolism in the tumor with [(18)F]-2-fluoro-2 deoxy-D-glucose (FDG) and positron emission tomography (FDG-PET) has been used to identify particularly aggressive tumors. The authors tested the hypothesis that both glucose transport and its metabolism play a key role in the progression of oral squamous cell carcinoma (OSCC). Retrospective analysis of Glut-1 expression was performed by immunohistology in 118 patients with OSCC, and a Glut-1 labeling index (LI) was established for each. A separate group of 44 patients with primary OSCC was evaluated prospectively by FDG-PET prior to surgery. To link the expression of Glut-1 with glucose metabolism, both FDG-PET and immunohistology were determined in a subgroup of 31 patients, and the results were correlated with overall survival. The patients who had OSCC with a low LI for Glut-1 survived significantly longer compared with patients who had OSCC with a high LI (138 months vs. 60 months; P = 0.0034). It was found that Glut-1 expression was an independent marker of prognosis in patients with OSCC. In patients who were evaluated by FDG-PET, the standardized uptake value (SUV) below the median split value of 5.6 was predictive of a longer survival (P < 0.027), whereas an SUV > 5.6 was associated with an increased hazard of death. In combination, a high Glut-1 level and a high SUV predicted shorter survival (P < 0.005) for patients with OSCC. Patients who achieved a complete response to preoperative radiation tended to have tumors with low glucose metabolism, as defined by both the Glut-1 LI and the SUV. Both glucose transport and glucose metabolism determine the glycolytic tumor phenotype, which is a significant negative biomarker of prognosis and overall survival in patients with OSCC.