A comprehensive study of HER2 aberration of gastric cancers in viewing as the target of molecular therapy

以胃癌 HER2 畸变作为分子治疗靶点的综合研究

• 批准号: 22590310
• 负责人: OOI Akishi
• 金额: $ 3万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590310/
• 关键词: 胃癌; HER2; 分子標的療法; 遺伝子増幅; FISH; ERBB2; 分子標的治療

By combined analysis of immunohistochemistry and fluorescence in situ hybridization (FISH) on 475 formalin-fixed paraffin-embedded tissue, 51 gastric adenocarcinoma with HER2-amplified cancer cells. The heterogeneity of HER2 amplification, if defined as the existence of less than 50% of cancer cells positive for ERBB2 amplification, the 21 tumors (42%) would be heterogeneous. The combined analysis of multiplex ligation-dependent probe amplification (MLPA) and FISH revealed that, co-amplification in individual cells of HER2 and MYC were found in 8 tumors and MYC/FGFR2, and MYC/EGFR in a case respectively. On the other hand, co-amplification of HER2/EGFR in 7, HER2/FGFR2 in one tumor and HER2/MET/FGFR2 in a tumor, however the respective genes were mutually exclusively amplified. In conclusion, the semi-comprehensive information of amplification status of HER2 and other genes obtained by the combined study of MLPA and FISH may be useful to plan individualized molecular target therapy against gastric cancers.

通过对 475 份福尔马林固定石蜡包埋组织进行免疫组织化学和荧光原位杂交 (FISH) 联合分析，发现 51 份带有 HER2 扩增癌细胞的胃腺癌。 HER2扩增的异质性，如果定义为存在少于50%的ERBB2扩增阳性癌细胞，则21个肿瘤（42%）将是异质的。多重连接依赖性探针扩增（MLPA）和FISH联合分析显示，8例肿瘤中发现HER2和MYC单个细胞共扩增，1例中分别发现MYC/FGFR2和MYC/EGFR。另一方面，7个肿瘤中的HER2/EGFR、一个肿瘤中的HER2/FGFR2和一个肿瘤中的HER2/MET/FGFR2共同扩增，然而，各个基因是相互排斥的扩增。总之，MLPA和FISH联合研究获得的HER2和其他基因扩增状态的半综合信息可能有助于规划针对胃癌的个体化分子靶向治疗。

项目成果

Genemplification of ERBB2 and EGFR in denocarcinoma insitu and ntramucosal adenocarciinoma of Barren's esophagus.

Barren食管原位腺癌和粘膜内腺癌中ERBB2和EGFR的基因扩增。

• 发表时间: 2010
• 影响因子: 2.2
• 作者: Ooi A.

Clinicopathological significance of platelet-derived growth factor(PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-beta phosphorylation, and microvessel density in gastric cancer.

胃癌中血小板源性生长因子（PDGF）-B和血管内皮生长因子-A表达、PDGF受体-β磷酸化和微血管密度的临床病理意义。

• 发表时间: 2010
• 影响因子: 3.8
• 作者: Suzulfl S.

Genomic copy-number alterations of MYC and FHIT genes are associated with survival in esophageal squamous-cell carcinoma

MYC 和 FHIT 基因的基因组拷贝数改变与食管鳞状细胞癌的生存相关

• DOI: 10.1016/j.humpath.2012.03.015
• 发表时间: 2012
• 影响因子: 5.7
• 作者: Miyawaki Y; Kawachi H; Ooi A; Eishi Y; Kawano T; Inazawa J; Imoto I
• 通讯作者: Imoto I

Multiplex ligation-dependent probe amplification法を用いた乳癌の遺伝子増幅の検討

使用多重连接依赖性探针扩增方法检查乳腺癌基因扩增

• 发表时间: 2012
• 作者: 大井章史

EGFR and HER2-Akt-mTOR signaling pathways are activated in subgroups of salivary gland carcinomas

EGFR 和 HER2-Akt-mTOR 信号通路在唾液腺癌亚组中被激活

• DOI: 10.1007/s00428-012-1282-3
• 发表时间: 2012
• 影响因子: 3.5
• 作者: Suzuki S; Dobashi Y; Minato H; Tajiri R; Yoshizaki T; Ooi A
• 通讯作者: Ooi A