June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Conjunctival melanomas exhibit decreased 5-hydroxymethylcytosine expression
Author Affiliations & Notes
  • Abraham Hang
    Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States
  • Tatyana Milman
    Wills Eye Hospital, Philadelphia, Pennsylvania, United States
  • Chenyan Lin
    Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Tzvete Dentchev
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Stephen Prouty
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Lily Wushanley
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Robyn Kweon
    Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • John T. Seykora
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Vivian Lee
    Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Abraham Hang, None; Tatyana Milman, None; Chenyan Lin, None; Tzvete Dentchev, None; Stephen Prouty, None; Lily Wushanley, None; Robyn Kweon, None; John Seykora, None; Vivian Lee, None
  • Footnotes
    Support  NEI K08-EY025742, Research to Prevent Blindness unrestricted departmental grant
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2841. doi:
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      Abraham Hang, Tatyana Milman, Chenyan Lin, Tzvete Dentchev, Stephen Prouty, Lily Wushanley, Robyn Kweon, John T. Seykora, Vivian Lee; Conjunctival melanomas exhibit decreased 5-hydroxymethylcytosine expression. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2841.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Conjunctival melanomas are relatively rare tumors, accounting for a small percentage of ocular melanomas. However, these tumors carry high morbidity and mortality rates, and early diagnosis and treatment are critical. Recent studies have identified 5-hydroxymethylcytosine (5hmC) as a potential diagnostic and prognostic biomarker in cutaneous melanoma. 5hmC is an epigenetic marker, generated from oxidation of 5-methylcytosine (5mC) by TET enzymes. It has been found at high levels in self-renewing and pluripotent stem cells, and has been postulated to regulate gene expression and initiate DNA methylation. We conducted a study to characterize the expression of 5hmC in benign conjunctival nevi, primary acquired melanosis (PAM) with moderate atypia, and conjunctival melanomas to determine whether 5hmC has utility in distinguishing benign from potentially malignant lesions.

Methods : A total of twelve samples were retrieved from archived cases, consisting of histopathologically confirmed benign nevi (n=4), PAM with moderate atypia (n=4), and conjunctival melanoma (n=4). All specimens were fixed in 10% buffered formalin and embedded in paraffin. Sections of 5 μm were cut, stained with hematoxylin and eosin (H&E), and reviewed by light microscopy. Sequential sections were then subjected to immunohistochemical staining with antibody against 5hmC. Negative and positive controls were performed in parallel. Slides were reviewed and graded by an ocular pathologist.

Results : All four nevi samples exhibited positive nuclear staining for 5hmC; in contrast, all four PAM specimens as well as three out of four conjunctival melanomas did not display staining for 5hmC (p=0.03). One melanoma specimen, rated as spindle cell, exhibited rare positive 5hmC staining.

Conclusions : This is the first study to-date which shows that 5hmC expression is significantly decreased in conjunctival melanomas when compared to benign nevi. In addition, specimens confirmed as PAM with moderate atypia exhibited negative staining for 5hmC, which may reflect their potential to progress to malignant melanoma. Future studies are needed to further delineate the level and specificity of 5hmC expression in different conjunctival melanocytic proliferations, as well as its utility as a clinical marker.

This is a 2021 ARVO Annual Meeting abstract.

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