CLINICAL RELEVANCE OF DNA-PLOIDY AND PROLIFERATIVE ACTIVITY IN CHILDHOOD RHABDOMYOSARCOMA - A RETROSPECTIVE ANALYSIS OF PATIENTS ENROLLED ONTO THE ITALIAN COOPERATIVE RHABDOMYOSARCOMA STUDY RMS88

Purpose: Evaluation of the possible clinical relevance of DNA ploidy a nd proliferative activity assessed as S-phase fraction (SPF) in childh ood rhabdomyosarcoma (RMS). Patients and Methods: We conducted a retro spective study on 59 RMS patients enrolled onto the ICS-RMS88 protocol (seven botryoid, 35 embryonal, and 17 alveolar RMS), for which formal in-fixed paraffin-embedded (FFPE) tissue was available. Nuclear suspen sions for cytometric investigation were obtained using a mechanical di saggregation, Tumors were distinguished according to their DNA index ( DI) value as follows: diploid (0.9 < DI < 1.1), hyperdiploid (1.1 less than or equal to DI < 1.8 or DI greater than or equal to 2.2), and te traploid (1.8 less than or equal to DI < 2.2); for analysis of SPF, a cutoff value of 14% was used. Results: DNA histograms were diploid in 19 (33%) cases, hyperdiploid in 29 (49%), and tetraploid in 10 (32%). One patient showed both a hyperdiploid and a tetraploid peek. The 5-ye ar overall survival (OS) rate by ploidy status was 73% in hyperdiploid patients as compared with 33% and 25% in diploid and tetraploid patie nts, respectively (P = .0012), A striking difference emerged when the 5-year OS for the combined diploid and tetraploid RMS groups was compa red with survival of the hyperdiploid RMS group: 30% versus 73%, respe ctively (P = .0006). In addition, the SPF was prognostically relevant: 5-year OS by SPF less than or greater than 14% was 70% and 36%, respe ctively (P = .009). Multivariate analysis confirmed the importance of DNA content (P = .0006) and SPF (P = .034) in predicting survival. Con clusion: These findings confirm that ploidy and SPF are important new prognostic factors that are able to identify selected groups of patien ts at high risk of treatment failure, even if the tumor's presentation is favorable according to standard criteria. (C) 1997 by American Soc iety of Clinical Oncology.