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5-Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms.
J Cutan Pathol 2017; 44(3):249-255JC

Abstract

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.

Authors+Show Affiliations

Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Melanoma Institute Australia, North Sydney, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Melanoma Institute Australia, North Sydney, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Discipline of Surgery, Royal Prince Alfred Hospital, Sydney, NSW, Australia.Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Melanoma Institute Australia, North Sydney, Australia. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28032662

Citation

Lee, Jonathan J., et al. "5-Hydroxymethylcytosine Is a Nuclear Biomarker to Assess Biological Potential in Histologically Ambiguous Heavily Pigmented Melanocytic Neoplasms." Journal of Cutaneous Pathology, vol. 44, no. 3, 2017, pp. 249-255.
Lee JJ, Vilain RE, Granter SR, et al. 5-Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms. J Cutan Pathol. 2017;44(3):249-255.
Lee, J. J., Vilain, R. E., Granter, S. R., Hu, N. R., Bresler, S. C., Xu, S., ... Lian, C. G. (2017). 5-Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms. Journal of Cutaneous Pathology, 44(3), pp. 249-255. doi:10.1111/cup.12880.
Lee JJ, et al. 5-Hydroxymethylcytosine Is a Nuclear Biomarker to Assess Biological Potential in Histologically Ambiguous Heavily Pigmented Melanocytic Neoplasms. J Cutan Pathol. 2017;44(3):249-255. PubMed PMID: 28032662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms. AU - Lee,Jonathan J, AU - Vilain,Ricardo E, AU - Granter,Scott R, AU - Hu,Nina R, AU - Bresler,Scott C, AU - Xu,Shuyun, AU - Frank,Alexander H, AU - Mihm,Martin C,Jr AU - Saw,Robyn P M, AU - Fletcher,Christopher D, AU - Scolyer,Richard A, AU - Murphy,George F, AU - Lian,Christine G, Y1 - 2017/02/06/ PY - 2016/08/03/received PY - 2016/11/03/revised PY - 2016/12/26/accepted PY - 2016/12/30/pubmed PY - 2017/8/16/medline PY - 2016/12/30/entrez KW - 5-hydroxymethylcytosine KW - MELTUMP KW - epigenetics KW - melanoma KW - pigmented epithelioid melanocytoma SP - 249 EP - 255 JF - Journal of cutaneous pathology JO - J. Cutan. Pathol. VL - 44 IS - 3 N2 - 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. SN - 1600-0560 UR - https://www.unboundmedicine.com/medline/citation/28032662/5_Hydroxymethylcytosine_is_a_nuclear_biomarker_to_assess_biological_potential_in_histologically_ambiguous_heavily_pigmented_melanocytic_neoplasms_ L2 - https://doi.org/10.1111/cup.12880 DB - PRIME DP - Unbound Medicine ER -