EGFR and ErbB2 mutation status in Japanese lung cancer patients
EGFR and ErbB2 mutation status in Japanese lung cancer patients
复制标题
DOI：
10.1002/ijc.21301
复制
发表时间：
2006-01-01
影响因子：
6.4
通讯作者：
Fujii, Y
中科院分区：
文献类型：
--
作者：
Sasaki, H;Shimizu, S;Fujii, Y
越来越多的证据表明，表皮生长因子受体（EGFR）及其家族成员与肺癌的发生和发展密切相关。在约25-40%的日本肺癌患者中发现EGFR基因的体细胞突变。最近，在大约4%的欧洲来源的肺癌患者中发现了erbB 2突变。我们调查了来自名古屋市立大学医院的95例手术治疗的非小细胞肺癌（NSCLC）患者的EGFR和erbB 2突变状态。纳入了75例腺癌病例。通过逆转录聚合酶链反应（RT-PCR）扩增和直接测序分析激酶结构域的EGFR和ernB 2突变的存在或不存在。我们还调查了27例手术治疗的NSCLC患者在接受吉非替尼治疗后的erbB 2突变状态，95例肺癌患者中有14例发现EGFR突变（CTG -> CGG; L 858 R）。我们还检测到9例患者的缺失Ia型突变和6例患者的缺失4型突变外显子19。在20号外显子中发现4个突变，其中2个为新突变，35例患者（36.8%）存在EGFR突变。这些突变状态与性别显著相关（女性73.3% vs.男性20%，p < 0.60011），吸烟状况（从不吸烟者69.4% vs.吸烟者16.9%，p < 0.0001），病理亚型（腺癌45.1%对非腺癌12.5%，p = 0.0089）和肺癌的分化状态（良好51%对中度或较差18.4%，p = 0.0021）。另一方面，erbB 2突变仅见于95例患者中的1例，位于第20外显子。该患者为女性，从不吸烟，患有腺癌。该12个核苷酸的插入突变（2324-2325 ins ATACGTGATGGC）位于激酶结构域（775-776 ins YVMA）的20号外显子。27例接受吉非替尼治疗的NSCLC患者中未发现erbB 2突变。总共，我们发现122例（0.8%）日本NSCLC患者中仅有I-erbB 2突变。EGFR突变型患者（13/25，52.0%）的erbB 2阳性（2+/3+）比率显著高于EGFR野生型患者（10/62，16.1%; p = 0.0247）。erbB 2突变的NSCLC标本呈I +免疫反应。EGFR突变状态可能与吉非替尼疗效良好的临床病理特征相关，如性别、吸烟史和肺癌病理亚型。然而，erbB 2突变在日本肺癌中罕见，其在分子靶向治疗中的价值有限。(c)2005 Wiley-Liss，Inc.
Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25-40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European-derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy-five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki-chuo Chest Medical Center.EGFR mutations (CTG -> CGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion la-type mutations from 9 patients and deletion 4-type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.60011), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p = 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p = 0.0021). On the other hand, erbB2 mutation was only found from I of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324-2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775-776 ins YVMA). There was no erbB2 mutation in 27 gefitinib-treated NSCLC patients. In total, we have found only I erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (2+/3+) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild-type patients (10/62, 16.1%; p = 0.0247). The NSCLC specimen with erbB2 mutation showed I + immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japnese lung cancer and is of limited value for molecular target therapy. (c) 2005 Wiley-Liss, Inc.