Expression of glucose transporter-1 is correlated with hypoxia-inducible factor 1α and malignant potential in pancreatic neuroendocrine tumors.

Abstract

The present study aimed to investigate the prognostic usefulness of the expression of glucose transporter type 1 (GLUT-1) and GLUT-2, hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor II messenger RNA-binding protein 3 (IMP3) in pancreatic neuroendocrine tumors (pNETs). Immunohistochemical staining for GLUT-1, GLUT-2, HIF-1α and IMP3 was performed in 70 pNET specimens. The expression of GLUT-1 and HIF-1α was significantly higher in the World Health Organization grade 2 (G2), neuroendocrine carcinoma cases and mixed-type pNETs compared with the G1 cases. Vessel invasion, a high Ki-67 labeling index and a high mitotic count were significantly more frequent in the GLUT-1- and HIF-1α-positive cases compared with the negative cases. Lymph node metastasis was significantly higher in the GLUT-1-positive cases than in the negative cases. Insulin expression was significantly higher in the IMP3-positive cases than the negative cases. The GLUT-1 expression group experienced a significantly poor disease-free survival rate compared with the negative GLUT-1 expression group. HIF-1α expression was significantly correlated with poor disease-free survival and overall survival rates. A multivariate analysis revealed that lymph node metastasis was an independent risk factor for disease-free survival in all cases. In the G1/G2 group, tumor size and lymph node metastasis were independent risk factors for disease-free survival. Overall, the results suggested that GLUT-1 is a useful prognostic biomarker for pNETs.