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

Am J Clin Pathol. 2014 Jul;142(1):121-32. doi: 10.1309/AJCPCX2D9YULBBLG.

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.

Keywords: MSH6; Melanoma; Mismatch repair; Survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adenosine Triphosphatases / metabolism
  • Adult
  • Aged
  • DNA Mismatch Repair*
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Male
  • Melanoma / metabolism*
  • Melanoma / mortality
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / metabolism
  • Nevus / metabolism*
  • Nuclear Proteins / metabolism
  • Prognosis
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / mortality
  • Survival Rate

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • Nuclear Proteins
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes