Liu Yan, Xu Mei Lin, Zhong Hao Hao, Heng Wan Jie, Wu Bing Quan
Department of Pathology, Peking University, Beijing, 100191, China.
Pathol Oncol Res. 2008 Dec;14(4):373-9. doi: 10.1007/s12253-008-9113-1. Epub 2008 Nov 5.
Somatic mutations in epidermal growth factor receptor (EGFR) tyrosine kinase domain, particularly deletions in exon 19 and point mutation in exon 21, are associated with clinical outcome in patients with lung adenocarcinoma, suggesting that EGFR mutation would have an important role in clinical decision making. DNA was extracted from the excised specimens of 60 lung adenocarcinoma patients with phenol-chloroform and ethanol precipitation. Exon 19 and 21 were amplified by PCR, and direct sequenced from both sense and antisense directions. EGFR somatic mutations were present in 13 of 60 patients (21.67%), including seven cases of in-frame deletion in exon 19 around codon 746 and six cases of amino acid substitution in exon 21. Exon 21 mutation is more frequent in adenocarcinomas with bronchi-alveolar component than exon 19 deletions. Mutations were more prevalent in well-differentiated adenocarcinomas (9/27, 33.33%) than in moderate to poor-differentiated adenocarcinomas (4/33, 12.12%) (P < 0.05). Adenocarcinomas with bronchi-alveolar components had higher mutation frequency (8/22,36. 36%) than those without bronchi-alveolar components (5/38, 13.16%) (P < 0.05). In this study, female patients had more mutation rate than male patients. This trend was also observed in the patients with pathologic stage I-II compared with stage III-IV, but neither of them was statistically significant. Patients with cisplatin-based adjuvant chemotherapy had no significantly prolonged survival compared with single radical resection. But patients with EGFR mutation had relative longer survival. In conclusion, our study suggest that EGFR mutations may be a valuable prognostic factor for disease free survival of surgically treated lung adenocarcinoma patients independently from adjuvant chemotherapy.
表皮生长因子受体(EGFR)酪氨酸激酶结构域的体细胞突变,尤其是外显子19缺失和外显子21点突变,与肺腺癌患者的临床预后相关,提示EGFR突变在临床决策中具有重要作用。采用酚-氯仿和乙醇沉淀法从60例肺腺癌患者的切除标本中提取DNA。通过PCR扩增外显子19和21,并从正反两个方向进行直接测序。60例患者中有13例(21.67%)存在EGFR体细胞突变,其中包括7例密码子746周围外显子19的框内缺失和6例外显子21的氨基酸替代。外显子21突变在具有支气管肺泡成分的腺癌中比外显子19缺失更常见。高分化腺癌(9/27,33.33%)中的突变比中低分化腺癌(4/33,12.12%)更普遍(P<0.05)。具有支气管肺泡成分的腺癌突变频率(8/22,36.36%)高于无支气管肺泡成分的腺癌(5/38,13.16%)(P<0.05)。在本研究中,女性患者的突变率高于男性患者。在病理分期为I-II期的患者与III-IV期患者中也观察到了这种趋势,但两者均无统计学意义。与单纯根治性切除相比,接受以顺铂为基础的辅助化疗的患者生存期并未显著延长。但EGFR突变患者的生存期相对较长。总之,我们的研究表明,EGFR突变可能是手术治疗的肺腺癌患者无病生存期的一个有价值的预后因素,独立于辅助化疗。