5-Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms. 2017

Jonathan J Lee, and Ricardo E Vilain, and Scott R Granter, and Nina R Hu, and Scott C Bresler, and Shuyun Xu, and Alexander H Frank, and Martin C Mihm, and Robyn P M Saw, and Christopher D Fletcher, and Richard A Scolyer, and George F Murphy, and Christine G Lian
Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

BACKGROUND 5-Hydroxymethylcytosine (5-hmC) is an epigenetic marker detectable through immunohistochemistry (IHC) that has been shown to distinguish benign nevi from melanoma with high sensitivity and specificity. The purpose of the study was to explore its diagnostic utility in a subset of histologically challenging, heavily pigmented cutaneous melanocytic neoplasms. METHODS 5-hmC IHC was performed on 54 heavily pigmented melanocytic tumors. Semi-quantitative analysis of immunoreactivity was correlated with clinical, pathologic and follow-up data. RESULTS Benign melanocytic neoplasms (4 of 4 blue nevi with epithelioid change; 12 of 12 combined nevi; 5 of 5 deep penetrating nevi, DPN) exhibited strong 5-hmC nuclear reactivity. Eight heavily pigmented blue nevus-like melanomas and 7 of 8 pigmented epithelioid melanocytomas (PEM) showed significant 5-hmC loss. Five of 7 atypical DPN cases and 8 of 10 melanocytic tumors of uncertain malignant potential (MELTUMP) showed low to intermediate 5-hmC immunoreactivity. These differences were statistically significant (P-value <.0001). CONCLUSIONS Loss of 5-hmC may be helpful in differentiating benign, diagnostically challenging, heavily pigmented melanocytic tumors from those with malignant potential. The intermediate to low 5-hmC immunoreactivity in atypical DPNs, PEMs and so-called MELTUMP categories further underscores the need to consider these neoplasms as having some potential for lethal biological behavior.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009508 Nevus, Pigmented A nevus containing melanin. The term is usually restricted to nevocytic nevi (round or oval collections of melanin-containing nevus cells occurring at the dermoepidermal junction of the skin or in the dermis proper) or moles, but may be applied to other pigmented nevi. Nevus, Melanocytic,Nevi, Melanocytic,Nevi, Pigmented,Pigmented Moles,Melanocytic Nevi,Melanocytic Nevus,Pigmented Nevi,Pigmented Nevus
D005260 Female Females
D005455 Fluorescent Antibody Technique Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy. Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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