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 and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, 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 months 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. Histologic 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. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.
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 and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several humancancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, 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 months 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. Histologic 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. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.
Authors: Edwin Choy; Francis Hornicek; Laura MacConaill; David Harmon; Zeeshan Tariq; Levi Garraway; Zhenfeng Duan Journal: Cancer Date: 2011-10-17 Impact factor: 6.860
Authors: Rex C Haydon; Andrea Deyrup; Akira Ishikawa; Robert Heck; Wei Jiang; Lan Zhou; Tao Feng; David King; Hongwei Cheng; Benjamin Breyer; Terrance Peabody; Michael A Simon; Anthony G Montag; Tong-Chuan He Journal: Int J Cancer Date: 2002-12-01 Impact factor: 7.396
Authors: Seth D Berman; Tina L Yuan; Emily S Miller; Eunice Y Lee; Alicia Caron; Jacqueline A Lees Journal: Mol Cancer Res Date: 2008-09 Impact factor: 5.852
Authors: N Entz-Werle; A Schneider; C Kalifa; A-C Voegeli; M-D Tabone; P Marec-Berard; L Marcellin; H Pacquement; P Terrier; P Boutard; N Meyer; M-P Gaub; P Lutz; A Babin; P Oudet Journal: Br J Cancer Date: 2003-06-16 Impact factor: 7.640