title: 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.affiliation: 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.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Larson
authors.affiliation: Department of Pathology, University of Massachusetts Medical Center, Worcester, MA, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Dresser
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lezcano
authors.affiliation: Department of Pathology, University of Massachusetts Medical Center, Worcester, MA, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Woda
authors.affiliation: Royal Prince Alfred Hospital, Melanoma Institute Australia and Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Benafsha
authors.initials: B
authors.lastname: Yosufi
authors.affiliation: Royal Prince Alfred Hospital, Melanoma Institute Australia and Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.affiliation: Royal Prince Alfred Hospital, Melanoma Institute Australia and Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.affiliation: Divison of Endocrinology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Yujiang G
authors.initials: YG
authors.lastname: Shi
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Christine Guo
authors.initials: CG
authors.lastname: Lian
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003596:Cytosine / Q000031:analogs & derivatives*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009506:Nevus / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine