High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma

Ester Alvino, Francesca Passarelli, Elda Cannavò, Cristina Fortes, Simona Mastroeni, Simona Caporali, Josef Jiricny, Gian Carlo Antonini Cappellini, Alessandro Scoppola, Paolo Marchetti, Andrea Modesti, Stefania D'Atri

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)121-132
Number of pages12
JournalAmerican Journal of Clinical Pathology
Volume142
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Melanoma
  • Mismatch repair
  • MSH6
  • Survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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