Mitsudomi T, Oyama T, Kusano T, Osaki T, Nakanishi R, Shirakusa T
Department of Surgery II, University of Occupational and Environmental Health, Kitakyushu, Japan.
J Natl Cancer Inst. 1993 Dec 15;85(24):2018-23. doi: 10.1093/jnci/85.24.2018.
Inactivation of the p53 tumor suppressor gene (also known as TP53) through a point mutation and/or loss of heterozygosity is one of the most common genetic changes found in various types of human tumors.
Our purpose was to investigate the relationship between the presence of p53 gene mutations and survival of patients with non-small-cell lung cancer (NSCLC) of all stages who underwent surgery with preoperative curative intent as a routine therapeutic intervention. The prognostic significance of factors like sex, age, tumor histology, and the stage of the disease was also evaluated.
We analyzed 120 tumor specimens from patients with histologically confirmed NSCLC for p53 mutations occurring in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism assay of genomic DNA. Univariate and multivariate analyses were performed to assess the association between p53 mutations and the survival of the NSCLC patients.
Fifty-one (43%) of 120 tumor specimens showed p53 mutations. Overall, the p53 mutations did not correlate with sex, age, or the clinical stage of the disease but showed frequent association with tumors of squamous cell histology. Univariate analysis revealed that the patients with p53 mutations survived for a significantly shorter period of time after surgery than those without the mutations (P = .0100, logrank test). The presence of p53 mutations was a significant prognostic factor in the patients with advanced disease (stages IIIA through IV) (P = .0091) but not in those with early disease (stages I and II) (P = .2837). Multivariate analysis using the Cox proportional hazards model found independent prognostic significance for p53 mutations (hazards ratio [HR] = 1.84; P = .018) and advanced disease stage (HR = 2.20; P = .003). The model also predicted the lower risk for female patients (HR = 0.51; P = .040).
The occurrence of p53 mutations in some NSCLC tumors may be independently associated with a shortened overall survival and may be of somewhat more prognostic significance in patients with advanced stage than in those with early stage of the disease.
Detection of p53 mutations may help in the selection of NSCLC patients suitable for appropriate investigational therapeutic strategies in view of improving their survival and quality of life.
通过点突变和/或杂合性缺失使p53肿瘤抑制基因（也称为TP53）失活是在各类人类肿瘤中发现的最常见的基因变化之一。
我们的目的是研究p53基因突变的存在与所有分期的非小细胞肺癌（NSCLC）患者生存之间的关系，这些患者接受了具有术前治愈意图的手术作为常规治疗干预。还评估了性别、年龄、肿瘤组织学和疾病分期等因素的预后意义。
我们通过对基因组DNA进行聚合酶链反应 - 单链构象多态性分析，分析了120例经组织学确诊的NSCLC患者的肿瘤标本中第5至8外显子发生的p53突变。进行单因素和多因素分析以评估p53突变与NSCLC患者生存之间的关联。
120例肿瘤标本中有51例（43%）显示p53突变。总体而言，p53突变与性别、年龄或疾病临床分期无关，但与鳞状细胞组织学肿瘤频繁相关。单因素分析显示，有p53突变的患者术后存活时间明显短于无突变的患者（P = 0.0100，对数秩检验）。p53突变的存在是晚期疾病（IIIA至IV期）患者的显著预后因素（P = 0.0091），但在早期疾病（I期和II期）患者中不是（P =0.2837）。使用Cox比例风险模型进行的多因素分析发现p53突变（风险比[HR]=1.84；P = 0.018）和晚期疾病分期（HR = 2.20；P = 0.003）具有独立的预后意义。该模型还预测女性患者风险较低（HR = 0.51；P = 0.040）。
一些NSCLC肿瘤中p53突变的发生可能与总生存期缩短独立相关，并且在晚期患者中可能比早期患者具有更大的预后意义。
鉴于改善NSCLC患者的生存和生活质量，检测p53突变可能有助于选择适合适当研究性治疗策略的患者。
