Molecular and Clinical database and Molecular Staging for Lung Cancer

就在这个项目启动后，表皮生长因子受体（EGFR）基因的突变被发现。因此，我们的主要工作是对EGFR、K-ras、p53和PIKsCA基因的突变分析及其临床意义。277例肺癌患者中有111例（40%）存在EGFR。外显子19缺失（47%）和21外显子858密码子点突变（44%）占突变的90%以上。EGFR突变在女性中显著高于男性，在不吸烟者中显著高于从不吸烟者，在腺癌中显著高于非腺癌（均P<0.001）。EGFR突变与K-ras突变具有互斥关系，而p53突变独立于EGFR突变发生。在接受吉非替尼治疗复发性疾病的59例患者中，33例存在EGFR突变。83%的EGFR突变患者和10例无EGFR突变患者对吉非替尼有反应。EGFR突变的患者存活时间明显更长。在该队列中，9例患者发现K-ras突变，这些患者对吉非替尼均无反应。这组患者的生存期较短。2例患者同时存在PIK3CA突变和EGFR突变。为了进一步建立临床数据库，我们还评估了转移淋巴结数量对患者生存的影响。转移淋巴结的数量被证明是有效的预后预测因子，并可能为目前的TNM分期系统提供进一步的信息。

Just after the initiation of this project, mutations of the gene for epidermal growth factor receptor (EGFR) were discovered. Accordingly, our main efforts were made on mutational analyses of the EGFR, K-ras, p53 and PIKsCA gene and their clinical implications.EGFR were present in 111 (40%) in 277 lung cancer cases. Exon 19 deletion (47%) and point mutation at codon 858 in exon 21 (44%) accounted for more than 90% of the mutations. EGFR mutations were siginificantly more frequent in women than men, in non-smokers than ever-smokers, and in adenocarcinoma than non-adenocarcinoma (all P<0.001). EGFR mutations and K-ras mutations had mutually exclusionary relationship, however, p53 mutations occurred independently of the EGFR mutations.In 59 patients who received gefitinib for their recurrent disease, EGFR mutations were present in 33. Response to gefitinib was observed in 83% of the patients with EGFR mutations and in 10 of those without EGFR mutation. Patients with EGFR mutations survived for a significantly longer period. In this cohort, K-ras mutations were found in 9 and none of these patients responded to gefitinib. Survival was shorter in this group of patients. Two patients had PIK3CA mutation as well as EGFR mutation.To further develop clinical database, we also evaluated effects of number of metastatic lymph nodes on patient survival. Number of metstatic node proved to be useful predictor of prognosis and may add further information to the current TNM staging system.