title: Diagnostic utility of 5-hydroxymethylcytosine immunohistochemistry in melanocytic proliferations.
abstract: Decreased hydroxymethylated cytosine (5-hydroxymethycytosine, 5-hmC) is reported to correlate with melanocyte dysplasia. The purpose of this study was to assess the diagnostic utility of this observation. 5-hmC immunohistochemistry was performed on tissue microarrays containing 171-melanocytic lesions from two different institutions. An immunohistochemical staining score representing the percentage and intensity of nuclear staining was assigned. The performance characteristics of 5-hmC immunohistochemistry for discriminating between a nevus and melanoma were determined. Additional cases of melanoma arising in a nevus (n = 8), nodal nevi (n = 5) and melanoma micrometastases to a lymph node (n = 6) were also assessed. Pronounced 5-hmC loss was observed in melanomas when compared with nevi (mean ± standard deviation = 6.71 ± 11.78 and 55.19 ± 23.66, respectively, p < 0.0001). While the mean immunohistochemical staining score values for melanocytic nevi and melanoma were distinct, there was considerable variability in immunohistochemical staining score within a single diagnostic category. The sensitivity and specificity of this assay for nevus vs. melanoma is 92.74 and 97.78%, respectively. Distinct biphasic staining patterns were observed in cases of melanoma arising in association with a nevus. Relative changes of 5-hmC expression within a single lesion may be more informative than absolute values when using 5-hmC as a diagnostic adjunct.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Rodić
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Zampella
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Reema
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.|The High Throughput Biology Center, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Burns
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.|Department of Dermatology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D009508:Nevus, Pigmented / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 5-hydroxymethylcytosine; dermatopathology; epigenetics; melanoma; nevus