Clinicopathological analysis of lung adenocarcinomas by EGFR gene mutation and gene expression analysis

肺腺癌的预后极差。本项目的目的是通过基因表达谱和免疫组化分析来鉴定分子靶向药物的候选分子。1肺腺癌中EGFR突变和癌胚蛋白GPC 3表达的分析：最近的研究包括我们的报告显示癌胚蛋白GPC 3在卵黄囊瘤、绒毛膜癌、畸胎瘤、肝细胞癌和肾母细胞瘤的肿瘤细胞中表达。从2005年和2006年东京大学医院病理科的档案中检索肺组织标本。32例标本可同时进行EGFR突变和GPC 3免疫组化分析。32例中EGFR突变11例（34%）。GPC 3阳性8例，其中6例为混合型腺癌，1例为粘液型实体腺癌，1例为高分化胎儿腺癌。在2例病例中，GPC 3表达和EGFR突变均为阴性。 ...更多信息 检测到离子。基因表达谱显示，GPC 3在18个肺腺癌细胞系中的一个中表达。这些结果表明，GPC 3在肺腺癌中的表达广泛地指示了胎儿型腺癌，并且GPC 3是有希望的分子靶向药物候选者。2在人肺腺癌中，最近的重要课题是EGFR激酶抑制剂吉非替尼和厄洛替尼的获得性耐药。替代组成型活性信号传导分子的候选者之一是c-met，而不是EGFR途径。12株肺腺癌细胞系中有5株c-Met呈组成性激活。c-Met过度表达的机制是有或无基因扩增、不依赖于配体和依赖于细胞-基质粘附。3肿瘤缺氧与癌细胞的恶性表型和患者预后不良相关。在A549肺腺癌细胞系中，缺氧诱导细胞运动，EGFR基因表达水平EGFR抑制剂AG 1478完全抑制缺氧诱导的细胞运动。少

Prognosis of lung adenocarcinomas is extremely poor. This project purpose is that the identification of the candidate molecules for molecularly-targeted drug by gene expression profile and immunohistochemical analyses.1 Analyses of EGFR mutation and oncofetal protein GPC3 expression in lung adenocarcinomas: Recent studies including our reports have shown the expression of oncofetal protein GPC3 in neoplastic cells of Yolk sac tumor, choriocarcinoma, teratoma, hepatocellular carcinoma, and Wilm's tumor. Lung tissue specimens were retrieved from the file of the Department of Pathology, Tokyo University Hospital in 2005 and 2006. The 32 samples could be analyzed both with EGFR mutation and GPC3 immunostaining. EGFR mutation was detected in 11 cases of 32 cases (34%). GPC3 was positive in 8 cases, including 6 adenocarcinomas with mixed subtypes, one solid adenocarcinoma with mucin production, and well differentiated fetal adenocarcinoma. In 2 cases, both week GPC3 expression and EGFR mutat … More ion were detected. Gene expression profile revealed the expression of GPC3 in the one of 18 lung adenocarcinomas cell lines. Those results suggested the GPC3 expression in lung adenocarcinomas broadly indicated the fetal type adenocarcinomas and GPC3 is promising candidate for molecularly-targeted drug.2 In human lung adenocarcinomas, recent important topic was the acquired resistance the EGFR kinase inhibitors, gefitinib and erlotinib. One of the candidates for alternative constitutive active signaling molecule is c-met, instead of EGFR pathway. Constitutive activation of c-Met was detected 5 out of 12 lung adenocarcinomas cell lines. The mechanisms c-Met overexpression were that either with or without gene amplification, ligand-independent and depends on cell-matrix adhesion.3 Tumor hypoxia is associated with a malignant phenotype of cancer cells and poor patient prognosis. In the A549 lung adenocarcinomas cell line, hypoxia induced the cell motility and EGFR gene expression level EGFR inhibitor AG1478 completely inhibited the promotion of cell motility induced by hypoxia. Less