Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma
Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma
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DOI：
10.1200/jco.1996.14.2.467
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发表时间：
1996-02-01
影响因子：
45.3
通讯作者：
Oberling, F
中科院分区：
文献类型：
--
作者：
Feugeas, O;Guriec, N;Oberling, F
目的：骨肉瘤的治疗主要是先化疗，再手术，术后再化疗。在诊断时，没有预后因素可以预测组织学反应和最终结果。视网膜母细胞瘤易感基因RB的失活与几种人类癌症的发病机制有关。在原发性骨肉瘤中，RB基因座的杂合性丢失（洛）超过60%。本研究的目的wets确定潜在的早期预后价值的洛RB基因的活检材料在diagnosis.Patients和方法：47例原发性骨肉瘤，在法国的四个机构，进行了研究。结果：仅在34例杂合子患者中检测到RB基因的洛。洛缺失24例（70%）。无洛患者的60个月无事件生存率（EFS）为100%，所有RB洛患者的EFS为43%，非转移性RB洛患者的EFS为65%。EFS的差异非常显著，分别为P = 0.008和P = 0.024。术前化疗后的组织学反应与洛状态无显著相关性。结论：RB基因洛是骨肉瘤的早期预测特征，提示潜在的不良结局。RE洛研究可能有助于早期发现高危患者。如果这一点得到证实，那么治疗就可以更早地适应个体的真实的复发风险。(C)1996年，美国临床肿瘤学会。
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 wets 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. RE 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. (C) 1996 by American Society of Clinical Oncology.