Larson, AllisonDresser, KarenZhan, QianLezcano, CeciliaWoda, Bruce A.Yosufi, BenafshaThompson, John F.Scolyer, Richard A.Mihm, MartinShi, YujiangMurphy, GeorgeLian, Christine2015-02-022013Larson, A. R., K. Dresser, Q. Zhan, C. Lezcano, B. A. Woda, B. Yosufi, J. F. Thompson, et al. 2013. “Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors.” Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 27 (7): 936-944. doi:10.1038/modpathol.2013.224. http://dx.doi.org/10.1038/modpathol.2013.224.0893-3952http://nrs.harvard.edu/urn-3:HUL.InstRepos:13890677DNA 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 to 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. 175 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 to 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.en-US5-hydroxymethylcytosineDNA methylationmelanocytic lesiondysplastic nevusmelanomaJournal Article2015-02-0210.1038/modpathol.2013.224