title: High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Institute of Translational Pharmacology, National Council of Research, Rome, Italy;
authors.forename: Ester
authors.initials: E
authors.lastname: Alvino
authors.affiliation: Histopathology Unit, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Passarelli
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland;
authors.forename: Elda
authors.initials: E
authors.lastname: Cannavò
authors.affiliation: Epidemiology Unit, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy;
authors.forename: Cristina
authors.initials: C
authors.lastname: Fortes
authors.affiliation: Epidemiology Unit, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy;
authors.forename: Simona
authors.initials: S
authors.lastname: Mastroeni
authors.affiliation: Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy;
authors.forename: Simona
authors.initials: S
authors.lastname: Caporali
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland;
authors.forename: Josef
authors.initials: J
authors.lastname: Jiricny
authors.affiliation: Department of Oncology and Dermatological Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy;
authors.forename: Gian Carlo Antonini
authors.initials: GC
authors.lastname: Cappellini
authors.affiliation: Department of Oncology and Dermatological Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scoppola
authors.affiliation: Department of Oncology, Sant'Andrea Hospital, University of Rome "La Sapienza," Rome, Italy; and.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata," Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
authors.affiliation: Laboratory of Molecular Oncology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy; s.datri@idi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Atri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D000368:Aged; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009506:Nevus / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: MSH6; Melanoma; Mismatch repair; Survival