TY - JOUR
T1 - The targetable epigenetic tumor protein EZH2 is enriched in intraocular medulloepithelioma
AU - Avedschmidt, Sarah E.
AU - Stagner, Anna M.
AU - Eagle, Ralph C.
AU - Harocopos, George J.
AU - Dou, Yali
AU - Rao, Rajesh C.
N1 - Funding Information:
Supported by the National Eye Institute (K12EY022299; Bethseda, MD, USA), National Cancer Institute-University of Michigan Comprehensive Cancer Center Support Grant (P30CA046592; Bethseda, MD, USA), The Leonard G. Miller Ophthalmic Research Fund at the Kellogg Eye Center (Ann Arbor, MI, USA), Barbara Dunn Research Fund (Ann Arbor, MI, USA), Beatrice & Reymont Paul Foundation (Bloomfield Hills, MI, USA), and March Hoops to Beat Blindness (RCR; Ann Arbor, MI, USA). The Leslie H. and Abigail S. Wexner Emerging Scholar Award of the A. Alfred Taubman Medical Research Institute, which supported, in part, this study (RCR). None of the sponsors participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Publisher Copyright:
© 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - PURPOSE. Intraocular medulloepithelioma (IM), the second most common primary neuroepithelial tumor of the eye, can lead to blindness in the affected eye and in rare cases, is deadly. Intraocular medulloepithelioma lacks targetable biomarkers for potential pharmacologic therapy. The purpose of this study was to identify actionable, tumor-specific proteins for potential diagnostic or therapeutic strategies. We hypothesize that the tumor-specific epigenetic enzyme EZH2 is selectively expressed in IM. METHODS. We conducted a retrospective case series study of five IM from five eyes of four children and one adult. Hematoxylin and eosin (H&E) stains of sections from formalin-fixed, paraffin-embedded blocks of IM tumors were used to localize IM tumor cells in each case. Using an EZH2-specific antibody for immunohistochemistry, we semiquantitatively calculated the proportion of IM tumor cells positive for EZH2, and also assayed for EZH2 staining intensity. RESULTS. We found that EZH2 was expressed in all IM cases but this protein was absent in nontumor ciliary body or retinal tissues. However, not all IM tumor cells expressed EZH2. Similar to retinoblastoma, moderately to poorly differentiated (primitive appearing) IM tumor cells strongly expressed EZH2; expression was weaker or absent in areas of well-formed neuroepithelial units. CONCLUSIONS. To our knowledge, this is the first study to identify an actionable tumor-specific maker, EZH2, in IM. Our findings point to the possibility of exploring the potential of EZH2 inhibitors, already in clinical trials for other cancers, for IM.
AB - PURPOSE. Intraocular medulloepithelioma (IM), the second most common primary neuroepithelial tumor of the eye, can lead to blindness in the affected eye and in rare cases, is deadly. Intraocular medulloepithelioma lacks targetable biomarkers for potential pharmacologic therapy. The purpose of this study was to identify actionable, tumor-specific proteins for potential diagnostic or therapeutic strategies. We hypothesize that the tumor-specific epigenetic enzyme EZH2 is selectively expressed in IM. METHODS. We conducted a retrospective case series study of five IM from five eyes of four children and one adult. Hematoxylin and eosin (H&E) stains of sections from formalin-fixed, paraffin-embedded blocks of IM tumors were used to localize IM tumor cells in each case. Using an EZH2-specific antibody for immunohistochemistry, we semiquantitatively calculated the proportion of IM tumor cells positive for EZH2, and also assayed for EZH2 staining intensity. RESULTS. We found that EZH2 was expressed in all IM cases but this protein was absent in nontumor ciliary body or retinal tissues. However, not all IM tumor cells expressed EZH2. Similar to retinoblastoma, moderately to poorly differentiated (primitive appearing) IM tumor cells strongly expressed EZH2; expression was weaker or absent in areas of well-formed neuroepithelial units. CONCLUSIONS. To our knowledge, this is the first study to identify an actionable tumor-specific maker, EZH2, in IM. Our findings point to the possibility of exploring the potential of EZH2 inhibitors, already in clinical trials for other cancers, for IM.
KW - EZH2
KW - Epigenetics
KW - Medulloepithelioma
UR - http://www.scopus.com/inward/record.url?scp=84995584893&partnerID=8YFLogxK
U2 - 10.1167/iovs.16-20463
DO - 10.1167/iovs.16-20463
M3 - Article
C2 - 27842164
AN - SCOPUS:84995584893
SN - 0146-0404
VL - 57
SP - 6242
EP - 6246
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 14
ER -