title: Proliferation characteristics in pediatric Hodgkin's lymphoma point to a cell cycle arrest in the G(1) phase.
abstract: This study was undertaken to determine the prognostic relevance of the proliferation rate in neoplastic cells in children and adolescents with Hodgkin's lymphoma. Paraffin-embedded biopsy specimens were immunostained with the proliferation-associated monoclonal antibodies Ki-S5 (Ki-67 antigen) and Ki-S2 (which detects the repp86 protein). Repp86 is a protein of about 100 kDa encoded by a gene located on human chromosome band 20q11.2. In contrast to the Ki-67 antigen, repp86 expression is restricted to the cell cycle phases G(2), S and M. Immunohistochemical results on diagnostic lymph node biopsy specimens from 224 patients included in two pediatric multicenter Hodgkin's trials, GPOH HD-90 and HD-95, were compared with clinical data. High Ki-67 antigen expression was a striking feature of Hodgkin's and Reed-Sternberg cells as well as lymphocytic and histiocytic cells (median: 80%, range: 20-100%), in contrast to low repp86 expression (median: 20%, range: 10-80%; P<0.001). The proliferation rate was independent of histological subtype, stage and presence of B symptoms. The probability of event-free and overall survival (+/-standard error) of all patients at 5 years was 91.6+/-2.0 and 98.1+/-1.0%, respectively. The proliferation rate of tumor cells did not influence the outcome. The difference between Ki-67 and repp86 expression in Hodgkin's and Reed-Sternberg or lymphocytic and histiocytic cells points to a possible cell cycle arrest in the G(1) phase, which may explain the obvious paradox of a highly proliferating but slowly growing paucicellular tumor. High Ki-67 expression does not seem to be an adverse prognostic factor in pediatric and adolescent patients with Hodgkin's lymphoma treated by effective risk-adapted chemo-radiotherapy regimens.
authors.affiliation: Department of Hematopathology, University of Kiel, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Tiemann
authors.forename: Alexander
authors.initials: A
authors.lastname: Claviez
authors.forename: Heike
authors.initials: H
authors.lastname: Lüders
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Günther
authors.initials: G
authors.lastname: Schellong
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörffel
authors.forename: Reza
authors.initials: R
authors.lastname: Parwaresch
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004720:Endonucleases; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D006689:Hodgkin Disease / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D016539:Reed-Sternberg Cells / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D004720:Endonucleases; C095221:SND1 protein, human