title: Evaluation of proliferative index and cell cycle protein expression in choroid plexus tumors in children.
abstract: Choroid plexus tumors are papillary neoplasms originating from the epithelium of the choroid plexus within the cerebral ventricles. They may be highly proliferative tumors, but detailed studies confirming their proliferative potential are lacking. Accordingly, we performed a clinicopathological correlation study of neoplasms arising from the choroid plexus in children using immunohistochemistry to characterize both their proliferative potential and their degree of cell cycle dysregulation when compared to non-neoplastic choroid epithelium. Twelve children with choroid plexus papillomas (CPPs) and 11 with choroid plexus carcinomas (CPCs) were identified from the time period 1982-1997. The outcome and survival of these children following treatment was determined from the medical record. Immunohistochemical studies were performed on CPPs and CPCs in this patient population and on non-neoplastic choroid epithelium using antibodies to MIB-1, p53, cyclin E, retinoblastoma protein (pRB), p107, and E2F-1. In 5 children with CPCs, tumor tissue was available for immunohistochemistry at a second surgery after cycles of chemotherapy had been given. The mean survival for patients with CPPs was 8.5 years, and with CPCs 5.2 years with a minimum follow-up of 4 years for the group. The expression of cell cycle markers and MIB-1 was greater in CPCs than in CPPs or normal choroid plexus. The expression of MIB-1, p53, pRB, and E2F-1 was significantly lower in patients with CPCs after chemotherapy than before. The MIB-1 labeling index for CPC patients who are alive and well after treatments was 15.19+/-3.2 compared to 22.63+/-3.04 for patients who have died from their disease (P<0.05). We conclude that CPCs in children are characterized by a higher MIB-1 labeling index and greater cell cycle dysregulation than are CPPs. Chemotherapy may work in part on CPCs to decrease their proliferative potential and expression of cell cycle regulatory proteins.
authors.affiliation: Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Carlotti
authors.forename: Bodour
authors.initials: B
authors.lastname: Salhia
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.forename: Mark
authors.initials: M
authors.lastname: Greenberg
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dirks
authors.forename: Warren
authors.initials: W
authors.lastname: Mason
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Becker
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
mesh_terms: D000293:Adolescent; D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins / Q000032:analysis*; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D019927:Cyclin E / Q000032:analysis; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis; D020288:Papilloma, Choroid Plexus / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D016160:Retinoblastoma Protein / Q000032:analysis; D050720:Retinoblastoma-Like Protein p107; D016019:Survival Analysis; D016708:Synaptophysin / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; C493844:RBL1 protein, human; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D016708:Synaptophysin; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53