Alterations in oncogenes and tumor suppressor genes on human lung cancer as a treament guideline

本研究的目的是研究人类肺癌中的各种基因损伤，并将其与包括患者预后在内的临床病理特征相关联。首先，我们检测了120例在福冈大学和日本职业与环境卫生大学(UOEH)手术的肺癌患者的p53突变。我们发现P53突变是一个不良的预后因素，特别是在晚期病例中。然而，这个队列来自两个机构，并不是完全连续的。下面的分析是对140名在大学附属医院接受治疗的连续患者中的129名患者进行的。我们分别使用免疫组织化学和SSCP分析在DNA和蛋白质水平上检查了这一队列中的P53异常。在这个队列中，p53突变是腺癌预后较差的因素，但对鳞癌的生存没有显著影响。然后，我们使用…检测了3p.5q，9p基因座的杂合性丢失与德克萨斯大学的阿迪·加兹达尔博士合作，获得了更多的微卫星多态性。LOH分别为51%、31%和23%。早期组3p LOH患者预后较差。然而，其他病变似乎与患者的预后无关。与贝勒医学院的威廉·本尼迪克特博士合作，用免疫组织化学方法检测了视网膜母细胞瘤基因的表达缺失。这种异常在22%的病例中被发现，但与患者的预后无关。包括上述基因病变在内的总生存率的多因素分析显示，完整的切除是预后不良的唯一决定因素。然而，对于I期患者的无病间期，多因素分析表明，3p杂合性缺失是唯一有意义的预测早期疾病复发的指标。然而，没有比常规使用的疾病分期等标记更好的遗传预后指标。较少

The objective of the present study is to investigate various genetic lesions in human lung cancer and to correlate the findings with clinicopathological features including patient prognosis.First, we examined 120 cases of lung cancer operated on at the Fukuoka University and the University of Occupational and Environmental Health, Japan (UOEH) for p53 mutations. We showed that p53 mutations were a poor prognostic factor especially in advanced cases. However, this cohort was from two institutions and was not fully consecutive. The following analysis was performed using 129 patients out of 140 consecutive patients who were treated at the UOEH.We examined this cohort for p53 abnormality at a DNA and protein level using immunohistochemistry and SSCP analysis, respectively. In this cohort, p53 mutations were a poor prognostic factor in adenocarcinoma, but there was no significant impact on survival in squamous cell carcinoma.We then examined loss of heterozygosity at the 3p.5q, 9p locus usi … More ng a microsatellite polymorphism in collaboration with Dr.Adi Gazdar at the University of Texas. LOHs were found in 51,31 and 23%, respectively. Patients with 3p LOH had a poor prognosis in early stage group. However, the other lesions seemed not to be correlated with patient prognosis. Loss of expression of retinoblastoma gene was examined using immunohistochemistry in collaboration with Dr.William Benedict at the Baylor College of Medicine. This abnormality was found in 22% of cases, butthere was no relationship with patient prognosis.Multivariate analysis for overall survival including above genetic lesions revealed that completeness of the resection was the only determinant for a poor prognosis. However, for a disease free interval in stage I patients, the multivariate analysis indicated that 3p LOH was the only significant predictor for an early disease relapse.In conclusion, p53 and 3p may be useful markers for clinical oncology of lung cancer. However, there were no genetic prognostic indicator superior to the marker such as a disease stage which are being used routinely. Less