TP53 mutations and outcome in osteosarcoma:: A prospective, multicenter study
TP53 mutations and outcome in osteosarcoma:: A prospective, multicenter study
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DOI：
10.1200/jco.2005.04.074
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发表时间：
2005-03-01
影响因子：
45.3
通讯作者：
Andrulis, IL
中科院分区：
文献类型：
--
作者：
Wunder, JS;Gokgoz, N;Andrulis, IL
目的 TP53 基因突变与多种不同恶性肿瘤的化疗耐药性以及不良预后相关。这是首个关于体细胞 TP53 突变对新诊断的四肢骨肉瘤患者预后价值的前瞻性研究。 患者和方法从 7 个三级医疗机构招募了 196 名四肢高级别非转移性骨肉瘤患者，并前瞻性观察肿瘤复发情况（中位随访时间为 44 个月）。所有患者均接受新辅助或辅助化疗和手术。通过聚合酶链反应单链构象多态性分析和直接DNA测序来分析肿瘤中TP53突变的存在。使用传统和组织学标志物作为预后因素的生存分析来检查 TP53 基因状态与系统复发风险的关联。结果患者年龄是随 TP53 基因状态变化的唯一因素 (P = .05)。 TP53 状态与系统性复发之间未发现任何关系（相对风险，1.24；P = .41）。基于错义或无义突变的分析给出了相似的结果 (P > .10)。在多变量分析中，肿瘤尺寸大（> 9 cm）（相对风险，1.9；P = .006）和对化疗的组织学反应差（小于或等于 90% 坏死）（相对风险，2.14；P = .02）是系统结果的唯一显着的独立预测因子。结论我们没有发现任何证据表明 TP53 突变可以预测高级别骨肉瘤患者发生转移。需要鉴定影响骨肉瘤化疗反应和临床结果的其他基因，以促进患者结果的进一步改善。
PurposeMutations of the TP53 gene have been associated with resistance to chemotherapy as well as poor prognosis in many different malignancies. This is the first prospective study of the prognostic value of somatic TP53 mutations in patients with newly diagnosed extremity osteosarcoma.Patients and MethodsOne hundred ninety-six patients with high-grade, nonmetastatic osteosarcoma of the extremities were enrolled from seven tertiary care institutions and observed prospectively for tumor recurrence (median follow-up duration, 44 months). All patients received neoadjuvant or adjuvant chemotherapy and surgery. Tumors were analyzed for the presence of TP53 mutations by polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing. The association of the status of the TP53 gene with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors.ResultsPatient age was the only factor that varied with TP53 gene status (P = .05). No relationship was identified between TP53 status and systemic relapse (relative risk, 1.24; P = .41). Analyses based on missense or nonsense mutations gave similar results (P > .10). In multivariate analysis, large (> 9 cm) tumor size (relative risk, 1.9; P = .006) and poor histologic response (less than or equal to 90% necrosis) to chemotherapy (relative risk, 2.14; P = .02) were the only significant independent predictors of systemic outcome.ConclusionWe found no evidence that TP53 mutations predict for development of metastases in patients with high-grade osteosarcoma. Identification of other genes that influence chemotherapy response and clinical outcome in osteosarcoma is needed to facilitate further improvements in patient outcomes.