title: Expression of stem cells markers in ocular hemangioblastoma associated with von Hippel-Lindau (VHL) disease.
abstract: OBJECTIVE
  To better understand the histogenesis of ocular hemangioblastomas associated with von Hippel-Lindau (VHL) disease.
  
  
  METHODS
  We found that co-expression of Epo and EpoR may mediate developmental stagnation and induce proliferation of hemangioblastoma. All lesions were frozen and/or fixed in formalin and embedded in paraffin. The specimens were sectioned and subjected to routine histology, immunohistochemistry and molecular analyses. Avidin-biotin-complex immunoperoxidase was used to evaluate the expression of erythropoietin (Epo), Epo receptor (EpoR), CD31, CD34, CD117, and CD133. Ocular hemangioblastoma cells were microdissected in order to determine expression of Epo and EpoR transcripts using reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Tumorlet-like cells were identified in retinal and optic nerve hemangioblastomas. Co-expression of Epo and EpoR at both protein and messenger levels was detected in many hemangioblastoma cells. In addition, ocular VHL lesions expressed several stem cell markers including CD133 to various degrees.
  
  
  CONCLUSIONS
  The data suggest that VHL disease-associated ocular hemangioblastomas are comprised of developmentally arrested stem cells including hemangioblasts, endothelial, and neuronal progenitor cells. We found that co-expression of Epo and EpoR may not only mediate developmental stagnation, but may also induce proliferation. Suppression of the growth of AC133/CD133 positive stem cells might be considered as one of the therapeutic targets for VHL-associated hemangioblastoma.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA. chanc@nei.nih.gov
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.forename: Defen
authors.initials: D
authors.lastname: Shen
authors.forename: Joseph
authors.initials: J
authors.lastname: Hackett
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D018325:Hemangioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D019574:Optic Nerve Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D019572:Retinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006623:von Hippel-Lindau Disease / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin