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

Research Project

Project/Area Number 17590293
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionChiba University

Principal Investigator

NAKATANI Yukio  Graduate School of Medicine, Chiba University, Department of Diagnostic Pathology, Professor, 大学院医学研究院, 教授 (20137037)

Co-Investigator(Kenkyū-buntansha) HIROSHIMA Kenzo  Chiba University, Department of Diagnostic Pathology, Graduate School of Medicine, Associate Professor, 大学院医学研究院, 助教授 (80218833)
MIYAGI Yohei  Kanagawa Prefectural Cancer Center, Clinical Research Laboratory, Chairman, がん分子病態部門, 部門長 (00254194)
NAGAI Yuichiro  Chiba University, Department of Molecular Pathology, Graduate School of Medicine, Assistant Professor, 大学院医学研究院, 助手 (10323396)
OIDE Takashi  Chiba University, Department of Diagnostic Pathology, Graduate School of Medicine, Assistant Professor, 大学院医学研究院, 助手 (00422246)
KOUCHI Katsunori  Tokyo Women's Medical University, Department of Pediatric Surgery, Yachiyo Medical Center, 八千代医療センター小児外科, 医師 (40312938)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsPathology / congenital cystic adenomatoid malformation / LKB1 / 先天性嚢胞性腺腫様肺奇形 / LKB1
Research Abstract

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.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (19 results)

All 2006 2005

All Journal Article (19 results)

  • [Journal Article] Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma : a morphological, immunohistochemical, and molecular analysis2006

    • Author(s)
      Kenzo Hiroshima
    • Journal Title

      Modern Patjology 19・10

      Pages: 1358-1368

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis.2006

    • Author(s)
      Kenzo Hiroshima, et al.
    • Journal Title

      Modern Pathology 19

      Pages: 1358-1368

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Distinction of pulmonary large ccell neuroendocrine carcinoma from small cell lung carcinoma : a morphological, immunohistochemical, and molecular analysis2006

    • Author(s)
      Kenzo Hiroshima
    • Journal Title

      Modern Pathology 19・10

      Pages: 1358-1368

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 肺芽腫の新展開2005

    • Author(s)
      中谷行雄
    • Journal Title

      呼吸 24・6

      Pages: 492-498

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Metastatic germ cell tumor of the lung masquerading as primary rhabdomyuosarcoma2005

    • Author(s)
      Randa Amin
    • Journal Title

      Pathology International 55・10

      Pages: 649-654

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytological characteristics of pulmonary large cell neuroendocrine carcinoma2005

    • Author(s)
      Kenzo Hiroshima
    • Journal Title

      Lung Cancer 48・3

      Pages: 331-337

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Aberrant methylation of SPARC in human lung cancers2005

    • Author(s)
      Makoto Suzuki
    • Journal Title

      British Journal of Cancer 92・5

      Pages: 942-948

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Epidermal growth factor receptor expression status in lung cancer correlates with its mutation2005

    • Author(s)
      Makoto Suzuki
    • Journal Title

      Human Pathology 36・10

      Pages: 1127-1134

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Frequency of loss of heterozygosity at 3 p, 13 q, and 17 p is related to proliferative activity in smoker with stage I non-small cell lung cancer2005

    • Author(s)
      Yukiko Haga
    • Journal Title

      Thoracic and Cardiovascular Surgery 53・2

      Pages: 114-117

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Recent advances in study of pulmonary blastoma.2005

    • Author(s)
      Yukio Nakatani, et al.
    • Journal Title

      Kokyu 24

      Pages: 492-498

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Metastatic germ cell tumor of the lung masquerading as primary rhabdomyosarcoma.2005

    • Author(s)
      Randa Amin, et al.
    • Journal Title

      Pathology International 55

      Pages: 649-654

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytological characteristics of pulmonary large cell neuroendocrine carcinoma.2005

    • Author(s)
      Kenzo Hiroshima, et al.
    • Journal Title

      Lung Cancer 48

      Pages: 331-337

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Aberrant methylation of SPARC in human lung cancers.2005

    • Author(s)
      Makoto Suzuki, et al.
    • Journal Title

      British Journal of Cancer 92

      Pages: 942-948

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Epidermal growth factor receptor expression status in lung cancer correlates with its mutation.2005

    • Author(s)
      Makoto Suzuki, et al.
    • Journal Title

      Human Pathology 36

      Pages: 1127-1134

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Frequency of loss of heterozygosity at 3 p, 9 p, 13 q, 17 p is related to proliferative activity in smokers with stage I non-small cell lung cancer.2005

    • Author(s)
      Yukiko Haga, et al.
    • Journal Title

      Thoracic and Cardiovascular Surgery 53

      Pages: 114-117

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Metastatic germ cell tumor of the lung masquerading as primary rhabdomyosarcoma2005

    • Author(s)
      Randa Amin
    • Journal Title

      Pathology International 55・10

      Pages: 6-6

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cytological characteristics of pulmonary large cell neuroendocrine carcinoma.2005

    • Author(s)
      Kenzo Hiroshima
    • Journal Title

      Lung Cancer 48・3

      Pages: 7-7

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Epidermal growth factor receptor expression status in lung cancer correlates with its mutation.2005

    • Author(s)
      Makoto Suzuki
    • Journal Title

      Human Pathology 36・10

      Pages: 8-8

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Frequency of Loss of Heterozygosity at 3p, 9p, 13q, and 17p is Related to Proliferative Activity in Smokers with Stage I Non-Small Cell Lung Cancer2005

    • Author(s)
      Yukiko Haga
    • Journal Title

      Thoracic and Cardiovascular Surgery 53・2

      Pages: 4-4

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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