Alsner J, Sørensen S B, Overgaard J
Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, Building 5, 8000, Aarhus C, Denmark.
Radiother Oncol. 2001 May;59(2):179-85. doi: 10.1016/s0167-8140(01)00301-2.
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.
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.
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.
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.
已有研究表明，TP53基因突变及p53的表达会影响头颈癌肿瘤细胞的放射敏感性。本研究旨在评估TP53突变是否会影响接受放疗或手术治疗的头颈癌患者的临床结局。
从放疗前采集的原发性活检组织的福尔马林固定石蜡包埋组织切片中提取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），并通过测序进行特征分析。患者接受单纯原发性放疗或手术治疗。根据丹麦头颈癌组（DAHANCA）方案进行治疗，每周放疗5或6次（每次2 Gy），总剂量为66 - 68 Gy。大多数患者还接受了乏氧放射增敏剂尼莫唑治疗。结果以5年精算值报告，并通过对数秩分析估计差异。
本分析基于1992年3月至1996年10月期间诊断的114例喉、咽和口腔鳞状细胞癌患者。90例患者仅接受原发性放疗，21例接受手术治疗。45例患者（39%）检测到TP53突变，在接受放疗的患者中，TP53突变与预后不良高度相关。TP53突变患者的局部区域控制率（5年精算值）为29%，而TP53野生型患者为54%（P < 0.01）。无病生存率的相应值分别为13%和38%（P < 0.01）。未发现相关性与特定的突变亚型（如影响DNA接触或锌结合区域的错义突变）有关，而是与任何突变的存在有关。相比之下，TP53突变不影响手术反应。
在接受原发性放疗而非手术治疗的头颈癌患者中，观察到TP53突变与预后不良（局部区域复发和死亡风险增加）之间存在密切关系。
