title: The Targetable Epigenetic Tumor Protein EZH2 is Enriched in Intraocular Medulloepithelioma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Avedschmidt
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States 3Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Stagner
authors.affiliation: Department of Ophthalmic Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, United States.
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Eagle
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States 6Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States.
authors.forename: George J
authors.initials: GJ
authors.lastname: Harocopos
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, United States 7Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, United States 8Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Yali
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, United States 8Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, United States 9Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States 10A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, Michigan, United States 11Section of Ophthalmology, Surgical Service, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan, United States.
authors.forename: Rajesh C
authors.initials: RC
authors.lastname: Rao
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000096:biosynthesis*; D057890:Epigenomics; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism* / Q000473:pathology; D019572:Retinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein