Proliferation Characteristics in Pediatric Hodgkin's Disease Point to a Cell Cycle Arrest in G1 Phase.

Abstract

This study was undertaken to determine the prognostic value of proliferation rate in Hodgkin and Reed-Sternberg (HRS) cells in pediatric and adolescent patients with Hodgkin's disease (HD).231 paraffin-embedded biopsies were immunostained with proliferation associated monoclonal antibodies Ki-S5 (Ki-67 antigen) and Ki-S2 (repp86 antigen), which is characterized by an expression pattern restricted to G2, S and M phases. Results were compared with clinical data from 224 patients included in multicenter GPOH HD-90 and HD-95 trials.High Ki-67 expression was a striking feature (median: 80%, range: 20–100%) in contrast to low Ki-S2 expression (median: 20%, range: 10–80%). Apoptosis was assessed in 133 patients by TUNEL method (median: 10%, range: <10–70%). Proliferation rate was independent of histological subtype, stage, presence of B symptoms and allocation to treatment group. Probability of event-free and overall survival at 5 years was 91% and 98%, respectively with no significant differences in patients with low or high proliferation rate.The difference between Ki-67 and repp86 expression in HRS cells points to a possible cell cycle arrest in G1 phase, which may explain the obvious paradoxon of a highly proliferating but slowly growing paucicellular tumor. High proliferation rate does not seem to be an adverse prognostic factor in pediatric patients with HD treated by effective chemoradiotherapy regimens.