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

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Abstract
BACKGROUND: 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 [18F]‐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).METHODS: 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.RESULTS: 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.CONCLUSIONS: 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. Cancer 2003;97:1015–24. © 2003 American Cancer Society.DOI 10.1002/cncr.11159