Metabolic Heterogeneity Confers Differences in the Tumor Microenvironment of Aggressive Types of Melanomas.

Abstract

Background: Melanoma affects skin and mucosa and can be particularly aggressive when the lesion is an advanced cutaneous tumor or located in the sinonasal or oral mucosa. Reprogramming of energy metabolism has been defined as a hallmark of cancer; so this study aimed to verify the expression of proteins related to metabolism and cellular proliferation.

Methods: Immunohistochemical analysis with antibodies adipophilin, FASN, GLUT-1, HIF-1α, and Ki-67 was performed in a series of 28 sinonasal melanomas (SM), 16 oral melanomas (OM), and 39 cutaneous melanomas (CM). For CM, 25 cases with matched lymph node metastases were analyzed, while 17 mucosal and 15 cutaneous melanocytic nevi served as controls.

Results: SM showed an increased frequency of undifferentiated cells, necrotic areas, and marked expression of adipophilin in comparison to OM. In metastatic CM, a significant increase of FASN expression was detected. However, the frequency of expression of this protein was not significantly different between primary tumors and their metastasis. Concerning adipophilin expression in CM with or without metastasis, no significant difference was found, whereas the Ki-67 proliferative index was significantly lower in metastatic tumors. Benign melanocytic lesions showed lower expression of all markers.

Conclusion: SM and OM show marked differences in metabolic phenotype alterations since SM are more frequently positive for adipophilin. In CM, the marked expression of FASN in metastatic tumors suggests that these proteins probably contribute to disease progression.