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Mod Pathol. 2014 Jul;27(7):936-44. doi: 10.1038/modpathol.2013.224. Epub 2014 Jan 3.

Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors.

Author information

1
1] Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA, USA.
3
Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
4
Royal Prince Alfred Hospital, Melanoma Institute Australia and Sydney Medical School, The University of Sydney, Sydney, Australia.
5
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
6
Divison of Endocrinology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

DNA methylation is the most well-studied epigenetic modification in cancer biology. 5-hydroxymethylcytosine is an epigenetic mark that can be converted from 5-methylcytosine by the ten-eleven translocation gene family. We recently reported the loss of 5-hydroxymethylcytosine in melanoma compared with benign nevi and suggested that loss of this epigenetic marker is correlated with tumor virulence based on its association with a worse prognosis. In this study, we further characterize the immunoreactivity patterns of 5-hydroxymethylcytosine in the full spectrum of melanocytic lesions to further validate the potential practical application of this epigenetic marker. One hundred and seventy-five cases were evaluated: 18 benign nevi, 20 dysplastic nevi (10 low-grade and 10 high-grade lesions), 10 atypical Spitz nevi, 20 borderline tumors, 5 melanomas arising within nevi, and 102 primary melanomas. Progressive loss of 5-hydroxymethylcytosine from benign dermal nevi to high-grade dysplastic nevi to borderline melanocytic neoplasms to melanoma was observed. In addition, an analysis of the relationship of nuclear diameter with 5-hydroxymethylcytosine staining intensity within lesional cells revealed a significant correlation between larger nuclear diameter and decreased levels of 5-hydroxymethylcytosine. Furthermore, borderline lesions uniquely exhibited a diverse spectrum of staining of each individual case. This study further substantiates the association of 5-hydroxymethylcytosine loss with dysplastic cytomorphologic features and tumor progression and supports the classification of borderline lesions as a biologically distinct category of melanocytic lesions.

PMID:
24390216
PMCID:
PMC4077910
DOI:
10.1038/modpathol.2013.224
[Indexed for MEDLINE]
Free PMC Article

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