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. 2016 Jun 2;15(11):1462-70.
doi: 10.1080/15384101.2016.1175258. Epub 2016 Apr 22.

The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4

Céline Pinheiro  1   2 , Vera Miranda-Gonçalves  3   4 , Adhemar Longatto-Filho  2   3   4   5 , Anna L S A Vicente  2 , Gustavo N Berardinelli  2 , Cristovam Scapulatempo-Neto  6 , Ricardo F A Costa  1 , Cristiano R Viana  6 , Rui M Reis  2   3   4 , Fátima Baltazar  3   4 , Vinicius L Vazquez  2   7
Affiliations

The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4

Céline Pinheiro et al. Cell Cycle. .

Abstract

BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.

Keywords: Cancer; Warburg effect; glycolysis; melanoma; monocarboxylate transporters.

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Figures

Figure 1.
Figure 1.
Immunohistochemical expression of MCT1 (A), MCT4 (B), GLUT1 (C) and CAIX (D) in melanoma. All the proteins were more importantly found in the plasma membrane of cells. (A) Stage IIC primary tumor; (B) Stage IIB primary tumor; (C) Distant metastasis; (D) Stage IV primary tumor.
Figure 2.
Figure 2.
Overall survival curves of melanoma's patients. The results are stratified according to protein immunohistochemical expression, using Kaplan Meier's method. Only significant results are shown. Continuous line refers to negative expression while interrupted line refers to positive expression. (A) Plasma membrane expression of MCT1; (B) Plasma membrane expression of MCT4.
Figure 3.
Figure 3.
Photomicrographs representative of weak (A), moderate (B) and strong (C) scores. MCT1 immunohistochemical staining in melanoma samples is shown.
See this image and copyright information in PMC

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