Biologic correlation between glucose transporters, hexokinase-II, Ki-67 and FDG uptake in malignant melanoma

Introduction: The purpose of this study was to investigate the correlative association between tumoral 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) uptake, and the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3 (GLUT-3), hexokinase II (HK-2), and Ki-67 expression in malignant melanoma.

Methods: Nineteen patients with histologically proven malignant melanoma and pretreatment FDG PET/CT performance were involved in this preliminary study. For semi-quantitative analysis of FDG PET/CT, maximal standardized uptake values (SUVmax) were estimated. Immunohistochemical staining of tumor sections was performed for GLUT-1, GLUT-3, and HK-2, and for the cell proliferation maker Ki-67. Especially, by combining proportions and intensity of immunochemical staining, we evaluated modified immunohistologic scores of GLUT-1 and GLUT-3.

Results: The SUVmax of malignant melanoma lesions ranged from 2 to 18.7 (average; 9.1±5.4). Comparison between nodal and extranodal lesions revealed no significant difference of SUVmax (p=0.97). GLUT-1 staining showed the most positive expression level (89.5%, 17/19) among the diverse immunohistochemical markers. There were significant relationships between FDG uptake of malignant melanoma and GLUT-1 proportion (p<0.0001), GLUT-1 intensity (p<0.0001), GLUT-3 proportion (p=0.031), GLUT-3 intensity (p=0.009), GLUT-1 immunohistologic scores (p<0.0001), and GLUT-3 immunohistologic scores (p=0.028). HK-2 was not expressed in all melanoma samples. Although Ki-67 expression showed a high grade in all staining, there was no significant link between FDG uptake and Ki-67 grades (p=0.38).

Conclusions: The data in this preliminary study indicate that FDG uptake in malignant melanoma is determined by GLUT-1 and GLUT-3, whereas HK-2 and Ki-67 play no role in FDG uptake of malignant melanoma.