LOSS OF HETEROZYGOSITY OF THE RB GENE IS A POOR PROGNOSTIC FACTOR IN PATIENTS WITH OSTEOSARCOMA

Purpose: The usual therapy of osteosarcoma is neoadjuvant-chemotherapy , followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response a nd final outcome. inactivation of the retinoblastoma-susceptibility ge ne RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus h as been found in greater than 60% of cases. The aim of this study wets to determine the potential early prognostic value of LOH of RB gene o n the biopsy material at diagnosis. Patients and Methods: Forty-seven patients with primary osteosarcoma, treated in four French institution s, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. Results: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 mont hs is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histolo gic response after preoperative chemotherapy did not show significant correlation with LOH status. Conclusion: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RE LOH study might shortly help to identify high- risk patients earlier. If this is verified, therapy could then be adap ted earlier to the individual's real risk of relapse. (C) 1996 by Amer ican Society of Clinical Oncology.