ErbB4 expression and mutation in Japanese patients with lung cancer
ErbB4 expression and mutation in Japanese patients with lung cancer
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DOI：
10.3816/clc.2007.n.027
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sasaki, Hidefumi;Okuda, Katsuhiro;Fujii, Yoshitaka
背景：大量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。近期，韩国肺癌患者中报道了erbB4激酶结构域突变。我们假设erbB4突变与肺癌的临床病理特征相关。
患者与方法：对名古屋市立大学医院105例手术治疗的非小细胞肺癌病例，通过逆转录聚合酶链反应扩增和直接测序分析erbB4激酶结构域突变的有无，其中包括63例腺癌病例。这105个样本的EGFR突变状态已有报道。我们通过免疫组织化学方法研究了40例非小细胞肺癌病例中erbB4的表达情况。
结果：105例肺癌患者中未发现erbB4突变。EGFR突变状态与性别（女性为74.2%，男性为9.5%；P < 0.0001）、吸烟状况（从不吸烟者为68.8%，吸烟者为11%；P < 0.0001）、病理亚型（腺癌为44.4%，非腺癌为4.8%；P < 0.0001）以及肺癌的分化状态（高分化为47.4%，其他为14.8%；P = 0.0004）显著相关。我们在20个样本中检测到erbB4蛋白阳性。erbB4蛋白状态与性别（女性为28.6%，男性为54.5%；P = 0.4075）、吸烟状况（从不吸烟者为69.4%，吸烟者为16.9%；P < 0.0001）、病理亚型（腺癌为46.2%，非腺癌为51.9%；P > 0.9999）或肺癌的分化状态（高分化为54.5%，其他为48.3%；P > 0.9999）无显著相关性。
结论：因此，erbB4突变在日本肺癌患者中罕见，对分子靶向治疗价值有限。
BACKGROUND: 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. Recently, erbB4 kinase domain mutations were reported in Korean patients with lung cancer. We hypothesized that erbB4 mutations correlate with clinicopathologic features of lung cancers. PATIENTS AND METHODS: The presence or absence of erbB4 kinase domain mutations was analyzed by reverse-transcription polymerase chain reaction amplification and direct sequencing in 105 surgically treated non-small-cell lung cancer cases from Nagoya City University Hospital. Sixty-three adenocarcinoma cases were included. The EGFR mutation status for these 105 samples were already reported. We have investigated erbB4 expression status by immunohistochemistry in 40 non-small-cell lung cancer cases. RESULTS: ErbB4 mutation was not found in 105 patients with lung cancer. The EGFR mutation status was significantly correlated with sex (women, 74.2% vs. men, 9.5%; P < 0.0001), smoking status (never-smokers, 68.8% vs. smokers, 11%; P < 0.0001), pathologic subtype (adenocarcinoma, 44.4% vs. non-adenocarcinoma, 4.8%; P < 0.0001), and differentiation status of the lung cancer (well-differentiated, 47.4% vs. others, 14.8%; P = 0.0004). We detected ErbB4 protein positivity in 20 samples. The ErbB4 protein status was not significantly correlated with sex (women, 28.6% vs. men, 54.5%; P = 0.4075), smoking status (never-smokers, 69.4% vs. smokers, 16.9%; P < 0.0001), pathologic subtype (adenocarcinoma, 46.2% vs. non-adenocarcinoma, 51.9%; P > 0.9999), or differentiation status of the lung cancer (well-differentiated, 54.5% vs. others, 48.3%; P > 0.9999). CONCLUSION: Thus, erbB4 mutations are rare in Japanese people with lung cancer and of limited value for molecular-targeted therapy.