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

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.

• Authors: Allison R Larson, Karen A Dresser, Qian Zhan, Cecilia Lezcano, Bruce A Woda, Benafsha Yosufi, John F Thompson, Richard A Scolyer, Martin C Mihm Jr, Yujiang G Shi, George F Murphy, Christine Guo Lian
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 27 Issue 7 Pg. 936-44 (Jul 2014) ISSN: 1530-0285 [Electronic] United States
• PMID: 24390216 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 5-hydroxymethylcytosine
• 5-Methylcytosine
• Cytosine

Topics

• 5-Methylcytosine (analogs & derivatives)
• Adult
• Aged
• Aged, 80 and over
• Cytosine (analogs & derivatives)
• DNA Methylation
• Female
• Humans
• Male
• Melanoma (genetics, pathology)
• Middle Aged
• Nevus (genetics, pathology)
• Precancerous Conditions (genetics, pathology)
• Skin Neoplasms (genetics, pathology)
• Young Adult