title: Immunohistochemical expression of cell-cycle regulators in pediatric embryonal brain tumors.
abstract: Embryonal tumors constitute the most common malignant brain tumor group in children. Experimental results indicate that genes involved in cell cycle and signal transduction are deregulated in medulloblastoma (MB) and atypical teratoid/rhabdoid tumors (AT/RT). The cell cycle is regulated by protein complexes composed of a regulatory subunit called Cyclin and a catalytic domain named Cyclin-dependent kinase (CDK). Cyclins and CDKs are in turn regulated by cyclin-dependent kinase inhibitors (CDKI) which inhibit cell-cycle progression. Cyclins D and Cyclin E are important for the passage of cells through G1 to S phase. P-27, a member of the universal CDKI family, is important in regulating the G1/S transition. Thus, the purpose of this study was to investigate the expression of p-27, Cyclin D3, and Cyclin E, and their possible prognostic significance in pediatric embryonal brain tumors. We retrospectively evaluated 51 children with embryonal tumors that were treated surgically in our institute. All patients had regular follow up examinations. The streptavidin-biotin HRP method was performed on paraffin sections for detection of p-27, Cyclin D3, and Cyclin E. There were 42 cases of MB and nine cases of AT/RT. Cyclin D3 expression was detected in 11/42 MB and 3/9 AT/RT patients. Cyclin E expression was detected in 28/42 MB and 8/9 AT/RT patients. High expression of Ki-67 (>50 %) and p-27 (>50 %) was observed in 23.8-73.8 % of MB patients. Combined high Ki-67 and p-27 expression was observed in 21.4 % cases of MB. In these cases there was expression of Cyclin E in 88.8 % and Cyclin D3 in 22.2 % of MB. No significant correlation was found between Ki-67 and p-27, Cyclin D3, and E. No correlation was found between Cyclin D3, Cyclin E, p-27, and overall survival. Increased p-27 and Cyclin E expression was detected in a substantial number of MB patients and in nearly all AT/RT patients. Further studies on a larger number of patients are needed to clarify a possible correlation of p-27 and Cyclin E with tumor behavior.
authors: Hematology Oncology Unit, 1st Department of Pediatrics, Athens University, Athens, Greece.
authors: Maria
authors: M
authors: Moschovi
authors: George A
authors: GA
authors: Alexiou
authors: Amalia
authors: A
authors: Patereli
authors: George
authors: G
authors: Siozos
authors: George
authors: G
authors: Sfakianos
authors: Neofytos
authors: N
authors: Prodromou
authors: Kalliopi
authors: K
authors: Stefanaki
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D056743:Cyclin D3 / Q000032:analysis / Q000096:biosynthesis*; D019927:Cyclin E / Q000032:analysis / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D056743:Cyclin D3; D019927:Cyclin E; D050760:Cyclin-Dependent Kinase Inhibitor p27