TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck
TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck
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DOI：
10.1016/s0167-8140(01)00301-2
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发表时间：
2001-05-01
影响因子：
5.7
通讯作者：
Overgaard, J
中科院分区：
文献类型：
--
作者：
Alsner, J;Sorensen, SB;Overgaard, J
背景和目的：TP 53基因突变和p53表达影响头颈部肿瘤细胞的放射敏感性。本研究旨在评估TP 53突变是否会影响头颈部肿瘤患者放疗或手术治疗的临床结果。材料和方法：从放疗前的原发性活检组织中提取DNA。使用变性梯度凝胶电泳（DGGE）作为初始扫描程序鉴定基因突变（外显子5-9），并通过测序进行表征。患者仅接受初次放疗或手术治疗。根据DAHANCA方案给予治疗，每周5次或6次（2戈伊）放疗（66-68戈伊）。大多数患者还接受了低氧放射增敏剂尼莫唑治疗。结果报告为5年的精算值，和差异估计log-rank analysis.Results：目前的分析是基于114例鳞状细胞癌的喉，咽和口腔诊断1992年3月至1996年10月。90例患者接受单纯放疗，21例患者接受手术治疗。TP 53突变在45例（39%）患者中发现，在接受放射治疗的患者中，TP 53突变与预后不良高度相关。TP 53突变的局部区域控制率（5年精算值）为29%，而TP 53野生型为54%（P < 0.01）。无病生存率分别为13%和38%（P < 0.01）。未发现相关性与特定突变亚型（例如影响DNA接触或Zn结合区域的错义突变）相关，而是与任何突变的存在相关。与此相反，TP 53突变并没有影响到响应surgery.Conclusions：TP 53突变和预后不良（局部区域失败和死亡的风险增加）的头颈部癌症患者给予初次放疗，但没有手术之间的密切关系。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Background and Purpose: TP53 gene-mutation and expression of p53 have been described to influence the radiosensitivity of tumour cells from head and neck carcinomas. The present study was performed to evaluate whether TP53 mutation may influence the clinical outcome of head and neck cancer patients treated with radiotherapy or surgery.Materials and methods: DNA was extracted from formalin-fixed paraffin-embedded tissue sections from primary biopsies taken before radiotherapy. Gene mutations (in exons 5-9) were identified using denaturing gradient gel electrophoresis (DGGE) as the initial scanning procedure and characterized by sequencing. Patients were treated with primary radiotherapy or surgery alone. Treatment was given according to the DAHANCA schedules with 5 or 6 weekly fractions (2 Gy) of radiotherapy (66-68 Gy). Most patients were also treated with the hypoxic radiosensitizer Nimorazole. The results are reported as 5-year actuarial values, and differences estimated by log-rank analysis.Results: The present analysis is based on 114 patients with squamous cell carcinoma of the larynx, pharynx and oral cavity diagnosed between March 1992 and October 1996. Ninety patients received primary radiotherapy alone and 21 were treated with surgery. TP53 mutations were found in 45 patients (39%) and in patients receiving radiotherapy, TP53 mutation was highly associated with poor prognosis. Loco-regional control rates (5-year actuarial values) for TP53 mutation was 29 vs. 54% for TP53 wildtype (P < 0.01). For disease-free survival the corresponding values were 13 and 38% (P < 0.01), respectively. The correlations were not found to be related to specific subtypes of mutations (e.g. missense mutations affecting DNA-contact or Zn-binding regions) but rather to the presence of any mutation at all. In contrast, TP53 mutation did not influence the response to surgery.Conclusions: A strong relationship was observed between TP53 mutation and poor prognosis (increased risk of loco-regional failure and death) in head and neck cancer patients given primary radiotherapy but not surgery. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.