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


Alvino, Ester; Passarelli, Francesca; Cannavò, Elda; Fortes, Cristina; Mastroeni, Simona; Caporali, Simona; Jiricny, Josef; Cappellini, Gian Carlo Antonini; Scoppola, Alessandro; Marchetti, Paolo; Modesti, Andrea; D'Atri, Stefania (2014). High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma. American Journal of Clinical Pathology, 142(1):121-132.

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.

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.

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2 citations in Web of Science®
3 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2014
Deposited On:14 Jul 2014 07:03
Last Modified:05 Apr 2016 17:57
Publisher:American Society for Clinical Pathology
ISSN:0002-9173
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1309/AJCPCX2D9YULBBLG
PubMed ID:24926095

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