Molecular analysis of etiological factors and malignant degrees for non-small cell lung cancer

对74例切除的鳞状细胞癌（sqs）和239例腺癌进行p53突变分析：然后检查sqs的肿瘤位置或腺癌亚型、吸烟和p53突变模式之间的关系，重点关注不同的病因。我们的假设是，p53基因的G→T转位是由烟草烟雾中所含的致癌物直接作用于DNA引起的，而基因CpG （CpG→A）位点的G→A转位是由内源性机制引起的。对相同的腺癌病例也进行了分析，以确定哪种类型的p53和k-ras联合突变状态更强烈地影响肿瘤的恶性。结果：1)Sqs按位置分为中心、中间和外围3种类型；中心型的CpG→A、中间型的G→T和其他外周型的突变频率最高。2)腺癌分为鞋钉状、柱状、杯状、多角形和混合型5种类型。其中，鞋钉型p53突变频率低，CpG→a率最高；柱状型和多角形型p53突变频率高，G→T率最高；混合型p53突变频率中等，其他碱基变化最高。3)非突变p53与k-ras合用的腺癌5年生存率最高，其次为突变p53与非突变k-ras合用，其次为非突变p53与突变k-ras合用，突变p53与k-ras合用的5年生存率最低。结果表明，sqs的发病部位和腺癌亚型不同，其病因也不同；最严重的恶性肿瘤是腺癌，p53和k-ras同时突变。

74 resected squamous cell carcinomas (sqs) and 239 adenocarcinomas were analyzed for p53 mutation : Any relationships between tumor location of sqs or subtype of adenocarcinomas, smoking, and p53 mutation patterns were then examined focusing on varying etiological factors. Our hypothesis was, that G→T transversion of p53 gene is caused by direct action of carcinogens contained in tobacco smoke on DNA, and that G→A transition at CpG (CpG→A) sites of the gene is caused by endogenous mechanisms. The same adenocarcinoma cases were also analyzed to determine what type of combined mutation status on p53 and k-ras affects malignancy of the tumors more strongly.Results:1) Sqs were divided into three types by location - central, intermediate and periphera l; the highest frequencies of CpG→A in the central type, G→T in the intermediate and other mutations in the peripheral, were observed. 2)Adenocarcinomas were divided into five types - hobnail, columnar, goblet, polygonal and mixed. Of these, the hobnail type showed a low p53 mutation frequency with the highest CpG→A rate, the columnar and polygonal types had a high mutation frequency with the highest G→T rates, and the mixed type showed intermediate frequency of p53 with the highest other base change. 3)Five year survival was the highest for adenocarcinomas with the combination of non-mutated p53 and k-ras, followed by the combination of mutated p53 and non-mutated k-ras, and then the combination of non-mutated p53 and mutated k-ras, with the combination of mutated p53 and k-ras having the lowest survival.The results show that etiological factors vary depending on locations of sqs and subtype of adenocarcinomas ; the worst malignancy was adenocarcinomas with the combined status on mutated p53 and k-ras.