Matrix metalloproteinases MMP-1, MMP-2, and MMP-13 are overexpressed in primary nodular melanoma

J Cutan Pathol. 2020 Feb;47(2):139-145. doi: 10.1111/cup.13603. Epub 2019 Nov 27.

Abstract

Background: The spread and invasion of malignant melanoma cells involve degradation and reorganization of the extracellular matrix by the activation of several matrix metalloproteinases (MMPs). This study analyzed the expression of MMP-1, MMP-2, and MMP-13 proteins in primary nodular melanoma (NM) and dysplastic nevi (DN) as a significant risk factor for melanoma development. The secondary goal was to analyze the correlation of MMPs protein expression in NM with tumor invasion, BRAF V600 mutation status, and overall survival.

Methods: Immunohistochemistry for MMP-1, MMP-2, and MMP-13 was performed on nodular melanoma (n = 52) and dysplastic nevi (n = 28) on tissue microarray (TMA). BRAF V600 mutation analysis on NM samples was performed by the Sanger sequencing method.

Results: A high level of MMPs expression in NM samples (>30%) compared with DN (<8%) was statistically significant (P < 0.001). BRAF V600 mutations were detected in 15 of 39 (38.5%) NM samples. This study revealed an interesting finding that MMP-1 and MMP-13 protein expression in the BRAF V600 mutated melanomas were significantly lower than in the BRAF V600 wild type (P < 0.05).

Conclusion: Cox analysis revealed that Clark categories, Breslow thickness, and MMP-1 high protein expression are predictive factors for shorter overall survival (P < 0.05).

Keywords: BRAF V600 mutation; dysplastic nevus; matrix metalloproteinase; nodular melanoma; overall survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 13 / biosynthesis*
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Melanoma* / enzymology
  • Melanoma* / pathology
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Skin Neoplasms* / enzymology
  • Skin Neoplasms* / pathology

Substances

  • Neoplasm Proteins
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP1 protein, human
  • Matrix Metalloproteinase 1