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5‐Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms
Author(s) -
Lee Jonathan J.,
Vilain Ricardo E.,
Granter Scott R.,
Hu Nina R.,
Bresler Scott C.,
Xu Shuyun,
Frank Alexander H.,
Mihm Martin C.,
Saw Robyn P.M.,
Fletcher Christopher D.,
Scolyer Richard A.,
Murphy George F.,
Lian Christine G.
Publication year - 2017
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.12880
Subject(s) - melanoma , pathology , immunohistochemistry , nevus , 5 hydroxymethylcytosine , medicine , blue nevus , biomarker , melanocytic nevus , dermatology , biology , cancer research , dna methylation , biochemistry , gene expression , gene
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.