Haneda Hiroshi, Sasaki Hidefumi, Lindeman Neal, Kawano Osamu, Endo Katsuhiko, Suzuki Eriko, Shimizu Shigeki, Yukiue Haruhiro, Kobayashi Yoshihiro, Yano Motoki, Fujii Yoshitaka
Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
Jpn J Clin Oncol. 2006 Feb;36(2):69-75. doi: 10.1093/jjco/hyi228. Epub 2006 Jan 31.
The presence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients has been reported to be higher in females, in non-smokers, in Japanese, and in adenocarcinoma patients, especially in bronchioloalveolar carcinoma (BAC). To further investigate the prevalence of EGFR mutations in relation to pathological factors, we evaluated EGFR mutations in series of Japanese adenocarcinoma patients who had never been treated with gefitinib.
In the previous studies, we examined mutation status in the tyrosine kinase domain of EGFR, exon18 through exon21, in 112 primary lung adenocarcinoma samples. Using these data, adenocarcinomas were histologically classified according to the presence or absence of bronchioloalveolar components.
Among 112 patients, 48 had adenocarcinoma with BAC components. Those with adenocarcinomas with BAC components had higher frequency of EGFR mutation (28/48, 58%) than those with non-BAC adenocarcinoma (24/64, 37%, P = 0.036). Male patients had the same trend; 12/23 (52%) male patients with adenocarcinoma with BAC components and 10/47 (21%) of those with non-BAC adenocarcinoma had EGFR mutation (P = 0.0135) but there was no correlation between the EGFR mutation status and with/without BAC components in 42 female patients (P = 0.30). Among 11 male non-smokers, patients with adenocarcinoma with BAC components had a tendency to have EGFR mutation more frequently than those with non-BAC adenocarcinoma (P = 0.061). In clear contrast, the frequency of EGFR mutation did not differ significantly between male smoker patients with adenocarcinoma with BAC components and those with non-BAC. Among patients with adenocarcinoma with BAC components, those with adenocarcinoma with EGFR gene mutation had a significantly better 5 year survival than those with adenocarcinoma with wild-type (85.7 versus 46.0%, P = 0.0017).
Adenocarcinomas with BAC components in male non-smokers seem to predict the presence of EGFR mutation. Half of female adenocarcinoma patients with EGFR mutation exhibit adenocarcinomas with non-BAC suggesting a different behavior from those in males. The prognosis of patients with adenocarcinoma with BAC components with EGFR gene mutation is predicted to be better than that of patients with adenocarcinoma with BAC components with wild-type EGFR gene.
据报道，在未接受过吉非替尼治疗的肺癌患者中，表皮生长因子受体（EGFR）突变在女性、非吸烟者、日本人以及腺癌患者中，尤其是细支气管肺泡癌（BAC）患者中更为常见。为了进一步研究EGFR突变与病理因素相关的患病率，我们评估了从未接受过吉非替尼治疗的一系列日本腺癌患者的EGFR突变情况。
在之前的研究中，我们检测了112例原发性肺腺癌样本中EGFR酪氨酸激酶结构域（外显子18至外显子21）的突变状态。利用这些数据，根据是否存在细支气管肺泡成分对腺癌进行组织学分类。
在112例患者中，48例患有伴有BAC成分的腺癌。伴有BAC成分的腺癌患者EGFR突变频率（28/48，58%）高于不伴有BAC的腺癌患者（24/64，37%，P = 0.036）。男性患者也有同样的趋势；12/23（52%）伴有BAC成分的男性腺癌患者和10/47（21%）不伴有BAC的腺癌患者发生EGFR突变（P = 0.0135），但在42例女性患者中，EGFR突变状态与是否伴有BAC成分之间无相关性（P = 0.30）。在11例男性非吸烟者中，伴有BAC成分的腺癌患者比不伴有BAC的腺癌患者更倾向于频繁发生EGFR突变（P = 0.061）。与之形成鲜明对比的是，伴有BAC成分的男性吸烟腺癌患者与不伴有BAC的患者之间EGFR突变频率无显著差异。在伴有BAC成分的腺癌患者中，伴有EGFR基因突变的腺癌患者5年生存率显著高于伴有野生型腺癌的患者（85.7%对46.0%，P = 0.0017）。
男性非吸烟者中伴有BAC成分的腺癌似乎预示着EGFR突变的存在。一半伴有EGFR突变的女性腺癌患者表现为不伴有BAC的腺癌，这表明其行为与男性不同。伴有BAC成分且具有EGFR基因突变的腺癌患者的预后预计优于伴有BAC成分且具有野生型EGFR基因的腺癌患者。
