High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma
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Published on: October 11, 2019
Ester Alvino1, Francesca Passarelli2, Elda Cannavò3
1From the Institute of Translational Pharmacology, National Council of Research, Rome, Italy;
Objectives:
The outcome of patients with primary melanoma (PM) cannot be completely explained based on currently adopted clinical-histopathologic criteria. In this study, we evaluated the potential prognostic value of mismatch repair protein expression in PMs.
Methods:
We examined the immunohistochemical staining of mismatch repair proteins in 18 benign nevi and 101 stage I to III PMs and investigated their association with tumor clinicopathologic variables and melanoma mortality.
Results:
Expression of MSH2, MLH1, and PMS2 was high in benign nevi and reduced in a subset of PMs. Conversely, MSH6 expression was absent or extremely low in benign nevi and increased in a subset of PMs. In the multivariate analysis, including sex, age, Breslow thickness, and ulceration, high MSH6 expression in PMs (ie, immunostaining in >20% of tumor cells) was significantly associated with an increased risk of melanoma mortality (relative risk, 3.76; 95% confidence interval, 1.12-12.70).
Conclusions:
MSH6 protein expression can be a valuable marker to improve prognosis assessment in PMs.
Insights
Mismatch repair protein MSH6 expression in primary melanoma (PM) may predict patient outcomes. High MSH6 levels in PMs were linked to increased melanoma mortality risk, suggesting its prognostic value.
Area of Science:
- Oncology
- Dermatology
- Molecular Pathology
Background:
- Current clinical-histopathologic criteria inadequately predict primary melanoma (PM) outcomes.
- Mismatch repair (MMR) proteins play a role in DNA repair and cancer development.
Purpose of the Study:
- To investigate the prognostic value of MMR protein expression in primary melanoma.
- To determine if MMR protein expression correlates with melanoma mortality.
Main Methods:
- Immunohistochemical staining for MMR proteins (MSH2, MLH1, PMS2, MSH6) was performed on 18 benign nevi and 101 primary melanomas (stages I-III).
- Associations between MMR protein expression, tumor clinicopathologic variables, and melanoma mortality were analyzed.
Main Results:
- MSH2, MLH1, and PMS2 expression was generally high in nevi and reduced in some PMs.
- MSH6 expression was low in nevi and increased in a subset of PMs.
- High MSH6 expression (>20% tumor cells) in PMs was significantly associated with increased melanoma mortality (RR 3.76; 95% CI 1.12-12.70) in multivariate analysis.
Conclusions:
- MSH6 protein expression is a potential prognostic marker for primary melanoma.
- Assessing MSH6 expression could enhance the prognostic accuracy beyond current clinical-histopathologic criteria.
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