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A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Matrix metalloproteinases MMP-1, MMP-2, and MMP-13 are overexpressed in primary nodular melanoma
Gordana Zamolo1,2, Maja Grahovac3, Gordana Žauhar4,5
1Department of Pathology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
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).
Insights
Matrix metalloproteinases (MMPs) are highly expressed in nodular melanoma compared to dysplastic nevi. High MMP-1 expression predicts shorter survival in melanoma patients.
Area of Science:
- Oncology
- Biochemistry
- Dermatology
Background:
- Malignant melanoma cell invasion involves extracellular matrix degradation mediated by matrix metalloproteinases (MMPs).
- This study investigates MMP-1, MMP-2, and MMP-13 protein expression in nodular melanoma (NM) and dysplastic nevi (DN).
- Assessing MMPs in NM correlates with tumor invasion, BRAF V600 mutation, and patient survival.
Purpose of the Study:
- To analyze MMP-1, MMP-2, and MMP-13 protein expression in primary nodular melanoma and dysplastic nevi.
- To determine the correlation between MMP protein expression in NM and clinicopathological factors including tumor invasion, BRAF V600 mutation status, and overall survival.
Main Methods:
- Immunohistochemistry was used to assess MMP-1, MMP-2, and MMP-13 protein expression in NM (n=52) and DN (n=28) samples using tissue microarray.
- BRAF V600 mutation analysis was performed on NM samples via Sanger sequencing.
Main Results:
- Significantly higher MMP expression was observed in NM samples (>30%) compared to DN (<8%) (P<0.001).
- BRAF V600 mutations were found in 38.5% of NM samples.
- MMP-1 and MMP-13 expression was significantly lower in BRAF V600 mutated melanomas versus wild-type (P<0.05).
Conclusions:
- High MMP-1 protein expression, along with Clark categories and Breslow thickness, are significant predictors of shorter overall survival in melanoma patients.
- MMPs play a crucial role in melanoma progression and prognosis.
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