Proliferation characteristics in pediatric Hodgkin's lymphoma point to a cell cycle arrest in the G 1 phase

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.