Expression of Glut-1 in Malignant Melanoma and Melanocytic Nevi: an Immunohistochemical Study of 400 Cases
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The glucose transporter-1 (Glut-1) is a cell membrane glycoprotein involved in glucose uptake. An increased expression of Glut-1 is an important cell adaptation mechanism against hypoxia. An upregulation of Glut-1 can be found in several types of malignant tumors, which are able to reprogram their metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect). However, the data regarding melanocytic lesions is equivocal. We performed comprehensive immunohistochemical analysis of the Glut-1 expression in 225 malignant melanomas (MM) and 175 benign nevi. Only the membranous expression of Glut-1 was regarded as positive. The expression of Glut-1 (the cut-off for positivity was determined as H-score 15) was found in 69/225 malignant melanomas. The number of positive cases and the H-score of Glut-1 increased where there was a higher Breslow thickness (p < 0.00001) when comparing pT1- pT4 MM groups. All benign nevi were classified as negative. In conclusion, the membranous expression of Glut-1 is a common feature of a malignant melanoma but this type of expression is very rare in benign melanocytic nevi. Our results suggest that the membranous expression of Glut-1 can be used as a surrogate marker in the assessing of the biological nature of benign and malignant melanocytic lesions. However, despite its high specificity, the sensitivity of this marker is relatively low. Moreover, due to the fact that the increased expression of Glut-1 correlates with a shorter survival period (10-year disease free survival, recurrence free survival and metastasis free survival and MFS), it can be used as a prognostically adverse factor.
KeywordsGlut-1 Malignant melanoma Melanocytic nevus Immunohistochemistry Follow-up
This work was supported by Ministry of Health, Czech Republic (Conceptual development of research organization 64,165, General University Hospital in Prague, and by project AZV 16-30954A), by Charles University (Project Progres Q28/LF1 and SVV 260367), and by OPPK (Research Laboratory of Tumor Diseases, CZ.2.16/3.1.00/24509). The funding bodies do not play any role in the design of the study and collection, analysis, and interpretation of the data and in writing of the manuscript.
Compliance with Ethical Standards
In compliance with the Helsinki Declaration, the project has been approved by Ethics Committee of the General University Hospital, Prague (reference number č.j. 56/15 Grant VES 2016 AZV 1. LF UK).
The authors declare that they have no competing interests.
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