Expression of Glut-1, HK-II, HIF-1 alpha, VEGF, p53 and Ki-67 in head and neck squamous cell carcinoma: Correlation with FDG uptake measured by PET Free

3812

Background: Positron emission tomography (PET) can be used to measure tumor metabolism by measuring the standard uptake value (SUV) of (F -18) fluorodeoxyglucose (FDG). However, increased but variable uptake of FDG has been noticed in head and neck tumors, and the mechanism of glucose entry into squamous cell carcinoma (SCC) remains unclear. This initial study compared FDG uptake with biomarkers expected to be involved in the underlying biologic mechanisms. Materials and Methods: Preoperative FDG PET scans were performed in 31 patients. FDG activity was assessed visually and quantitatively. Deparaffinized, formalin-fixed sections were immunostained with antibodies to glucose transporter-1 (Glut-1); hexokinase (HK) II; hypoxia-inducible factor-1-alfa (HIF-1alpha); vascular endothelial growth factor (VEGF), P53 and Ki-67. Mitotic activity index (MAI) and amount of necrosis were also assessed. Results: There were positive correlations between FDG uptake and Glut-1 expression (P< 0.05), MAI (P< 0.04), Ki-67 (P< 0.05), P53 (P< 0.02), amount of necrosis (P< 0.03), number of tumor cells/volume (P< 0.01), expression of microvessel density (P =0.05). HIF-1alpha, VEGF, HK II showed no univariate correlation with FDG. In logistic regression, however, HIF-1alpha and HK II added value to Glut-1. Conclusion: FDG uptake in head and neck SCC is a function of microvasculature for delivering nutrients, Glut-1 for transportation of FDG into the cell, HK for entering FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis) and HIF-1alpha for upregulating Glut-1. These features are helpful for the better understanding why SCC vary in FDG uptake and elucidate the low uptake in some cases.