molecular and pathological study on pathogenesis of cystic lung diseases : Analysis of congenital cystic adenomatoid malformation as a model.

囊性肺疾病发病机制的分子和病​​理学研究：以先天性囊性腺瘤样畸形为模型的分析。

• 批准号: 17590293
• 负责人: NAKATANI Yukio
• 金额: $ 1.92万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590293/
• 关键词: Pathology; congenital cystic adenomatoid malformation; LKB1; 先天性嚢胞性腺腫様肺奇形; LKB1

1) Direct sequencing analysis of LKB1 gene revealed no mutation in the exon 1, 2, and 4 of LKB1 on the genomic DNA obtained from two patients having congenital cystic adenomatoid malformation (CCAM).2) Immunohistochemical analysis for LKB1, phospho-mammalian target of rapamycin (p-mTOR), phospo-ribosomal protein S6 (p-S6), p63, and high molecular weight cytokeratin (CK34 β E12) was performed using formalin-fixed and paraffin-embedded lung sections obtained from seven CCAM patients. In the normal region of the lung, bronchi showed immunoreactivity for the anti-LKB1 antibody mainly in the basal layer of the columnar epithelium, whereas no obvious LKB1-immunoreactivity was observed in the cystic lesion lined by bronchiole-like cuboidal and/or columnar epithelium. The basal cells labeled with anti-p63 and anti-CK34 β E12 antibodies were observed in the cystic CCAM lesions almost same as those in normal regions, suggesting that the decreased LKB1-immunoreactivity in the cystic CCAM lesion was not due to reduced basal cells. Anti-p-mTOR antibody yielded no apparent immunohistochemical staining. Immunoreactivity for anti-p-S6 antibody tended to be increased in the epithelial cells of CCAM lesions as compared with those in normal regions. These results suggest that LKB1 and/or some related proteins involved in the signaling pathway regulating cell proliferation could be altered in CCAM.3) For the purpose of clonality analysis for CCAM, mathylation-specific polymerase chain reaction (MSP) for human androgen receptor gene (HUMARA) was tested. MSP was proved to be useful for detecting monoclonality of lung carcinoma tissue. We are analyzing CCAM lesions with MSP to clarify whether the airway-type epithelial cells are monoclonally proliferated or not.

1)对2例先天性囊性腺瘤样畸形患者的LKB1基因外显子1、2、4进行直接测序分析。2.用福尔马林固定石蜡包埋的7例先天性囊性腺瘤样畸形患者肺组织切片，进行LKB1、雷帕霉素磷酸化靶标蛋白(p-mTOR)、磷酸化核糖体蛋白S6(p-S6)、p63和高分子量细胞角蛋白(CK34βE12)的免疫组织化学检测。在正常肺组织中，抗LKB1抗体的免疫反应主要位于柱状上皮的基底层，而在以细支气管样立方和/或柱状上皮为衬里的囊性病变中，未见明显的LKB1免疫反应。囊性癌组织中可见抗p63和抗CK34βE12抗体标记的基底细胞，与正常组织基本一致，提示囊性病变中LKB1免疫反应性降低不是由于基底细胞减少所致。抗p-mTOR抗体未见明显免疫组织化学染色。CCAM病变区上皮细胞中抗p-S6抗体免疫反应性较正常区明显增强。这些结果提示CCAM中参与调控细胞增殖信号通路的LKB1和/或相关蛋白可能发生改变。3)为了对CCAM进行克隆性分析，对人雄激素受体基因(HUMARA)进行了甲基化特异性聚合酶链式反应(MSP)检测。MSP可用于检测肺癌组织的单克隆性。我们正在分析合并MSP的CCAM病变，以明确气道型上皮细胞是否单克隆性增殖。

项目成果

Metastatic germ cell tumor of the lung masquerading as primary rhabdomyosarcoma

伪装成原发性横纹肌肉瘤的肺转移性生殖细胞肿瘤

• 发表时间: 2005
• 期刊: Pathology International 55・10
• 作者: Tanaka-Fujita;R.;Soeno;Y;Satoh;H.;Nakamura;Y. and Mori;S.;Randa Amin
• 通讯作者: Randa Amin

肺芽腫の新展開

肺母细胞瘤的新进展

• 发表时间: 2005
• 期刊: 呼吸 24・6
• 作者: Nishime C.;Kijima H.;et al.;Ikeda R;Kaname et al.;中谷行雄
• 通讯作者: 中谷行雄

Epidermal growth factor receptor expression status in lung cancer correlates with its mutation.

• DOI: 10.1016/j.humpath.2005.08.007
• 发表时间: 2005-10
• 期刊: Human pathology
• 影响因子: 3.3
• 作者: Makoto Suzuki;H. Shigematsu;K. Hiroshima;T. Iizasa;Y. Nakatani;J. Minna;A. Gazdar;T. Fujisawa

Distinction of pulmonary large ccell neuroendocrine carcinoma from small cell lung carcinoma : a morphological, immunohistochemical, and molecular analysis

肺大细胞神经内分泌癌与小细胞肺癌的区别：形态学、免疫组织化学和分子分析

• 发表时间: 2006
• 期刊: Modern Pathology 19・10
• 作者: Wang T;et al.;Kenzo Hiroshima
• 通讯作者: Kenzo Hiroshima

Aberrant methylation of SPARC in human lung cancers

人类肺癌中 SPARC 的异常甲基化

• 发表时间: 2005
• 期刊: British Journal of Cancer 92・5
• 作者: Zheng CL.;Su nizawa T.;Che XF.;Tsuyama S.;Furukawa T.;Haraguchi M.;Gao H.;Gotanda T.;Jueng HC.;Murata F.;Akiyama S.;Makoto Suzuki
• 通讯作者: Makoto Suzuki