2000 Fiscal Year Annual Research Report

遺伝子診断の導入による新しい乳癌診療体系の確立

Research Project

Project/Area Number	11307019
Research Institution	Osaka University
Principal Investigator	野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)
Co-Investigator(Kenkyū-buntansha)	丹治芳郎大阪大学, 医学系研究科, 助手 (90263269) 田口哲也大阪大学, 医学系研究科, 講師 (80243260) 芝英一大阪大学, 医学系研究科, 助教授 (90215997) 塚本文音大阪大学, 医学系研究科, 助手 (70303964) 三好康雄大阪大学, 医学系研究科, 助手 (50283784)
Keywords	乳癌 / 遺伝子診断 / 微小転移 / 遺伝性乳癌 / 抗癌剤感受性
Research Abstract	遺伝子診断の乳癌診療への応用を目指して研究を進めている。以下に、現在までの研究成果を要約する。(1)FISH法(1、11、17番染色体の数的異常の検出)による乳癌の鑑別診断:穿刺細胞診検体(n=176)を用いたFISH法による乳腺腫瘍の良悪性の鑑別診断法が、通常の細胞診(86.4%)と同等の正診率(91.5%で)を有すること、また、chromosomal instability(CIN)とリンパ節転移が有意の相関を示し、CINが乳癌の新しい悪性度の指標となる得ることを明らかとした。(2)Cytokeratin(CK)19mRNA RT-PCRによる乳癌の微小骨髄転移の診断:CK19mRNAをターゲットとした定量的RT-PCR(Taq-Man法)によって検出される骨髄微小転移が乳癌の独立した予後因子であることを明らかとした。また、mammaglobinあるいはCEAのmRNAをターゲットとしたRT-PCRも、骨髄・リンパ節の微小転移の検出に有用であることを示した。(3)家族性乳癌の遺伝子診断:乳癌家系(n=113)の発端者より採血してBRCA1およびBRCA2を解析した結果、BRCA1の変異が15家系、BRCA2の変異が21家系に同定された。卵巣癌患者が存在する家系。第一度近親者に三人以上乳癌患者が存在する家系、両側性乳癌患者が存在する家系、若年発症患者(40歳以下)が存在する家系ではBRCA1またはBRCA2に変異を有する頻度がそれぞれ58.3%、36%,40%、38%と高率であった。(4)抗癌剤感受性の診断:進行・再発乳癌を対象として、[99m]Tc-MIBIシンチグラフィーの抗癌剤感受性診断における有用性を検討したところ、docetaxel(DOC)およびcyclophosphamide+epirubicin(CE)に対する乳癌の感受性診断に有用であることを明らかにした(正診率=89.1%)。また、collagen gel droplet embedded culture-drug sensitivity test(CD-DST)についても同様の検討を行った結果、高い正診率(91.8%)を得ることができた。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Miyoshi,Y., et al.: "Breast Cancer Risk Associated with Polymorphism in CYP19 in Japanese Women."Int J Cancer. 89・4. 325-328 (2000)
[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability by Loss of BRCA1 Expression and p53 Abnormality in Sporadic Breast Cancers."Cancer Lett. 159・2. 211-216 (2000)
[Publications] Tsukamoto,F., et al.: "Detection of Chromosomal Aneusomy by Fluorescence In Situ Hybridization in Fine Needle Aspirates from Breast Tumors : Application to Preoperative Diagnosis of Cancer."Cancer Cytopathol. (in press). (2000)
[Publications] Ikeda,N., et al.: "Prognostic Significance of Occult Bone Marrow Micrometastases of Breast Cancer Detected by Quantitative Polymerase Chain Reaction for Cytokeratin 19 mRNA."Jpn J Cancer Res. 91. 918-924 (2000)
[Publications] Ikeda,N., et al.: "Frequency of BRCA1 and BRCA2 Germline Mutations in Japanese Breast Cancer Families."Int J Cancer. (in press).
[Publications] Kim,SJ., et al.: "Detection of Breast Cancer Micrometastases in Peripheral Blood Using Immunomagnetic separation and immunocytochemistry."Breast Cancer. (in press).
[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-b Messenger RNA and its Variants in Human Breast Cancers."Int J Cancer. (in press). (2000)
[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-a and -b Messenger RNA Expression in Human Breast Cancers by Real-time Polymerase Chain Reaction."Cancer. (in press). (2000)
[Publications] Miyoshi,Y., et al.: "Genetic Polymorphism in CYP17 and Breast Cancer Risk in Japanese Women."Eur J Cancer. (in press). (2000)
[Publications] Miyoshi,Y., et al.: "Association of Centrosomal Kinase STK15/BTAK mRNA Expression with Chromosomal Instability in Human Breast Cancers."Int J Cancer. (in press). (2000)
[Publications] Tsukamoto,F., et al.: "Clinicopathological Analysis of Breast Cancers with Chromosomal Aneusomy Detected by Fluorescence In Situ Hybridization."Cancer Cytopathol. (in press).
[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability of BRCA1-Associated Hereditary Breast Cancers by p53 Abnormality."Breast Journal. (in press).

2000 Fiscal Year Annual Research Report

遺伝子診断の導入による新しい乳癌診療体系の確立

Principal Investigator

野口 眞三郎 大阪大学, 医学系研究科, 教授 (10303942)

Research Products

[Publications] Miyoshi,Y., et al.: "Breast Cancer Risk Associated with Polymorphism in CYP19 in Japanese Women."Int J Cancer. 89・4. 325-328 (2000)

[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability by Loss of BRCA1 Expression and p53 Abnormality in Sporadic Breast Cancers."Cancer Lett. 159・2. 211-216 (2000)

[Publications] Tsukamoto,F., et al.: "Detection of Chromosomal Aneusomy by Fluorescence In Situ Hybridization in Fine Needle Aspirates from Breast Tumors : Application to Preoperative Diagnosis of Cancer."Cancer Cytopathol. (in press). (2000)

[Publications] Ikeda,N., et al.: "Prognostic Significance of Occult Bone Marrow Micrometastases of Breast Cancer Detected by Quantitative Polymerase Chain Reaction for Cytokeratin 19 mRNA."Jpn J Cancer Res. 91. 918-924 (2000)

[Publications] Ikeda,N., et al.: "Frequency of BRCA1 and BRCA2 Germline Mutations in Japanese Breast Cancer Families."Int J Cancer. (in press).

[Publications] Kim,SJ., et al.: "Detection of Breast Cancer Micrometastases in Peripheral Blood Using Immunomagnetic separation and immunocytochemistry."Breast Cancer. (in press).

[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-b Messenger RNA and its Variants in Human Breast Cancers."Int J Cancer. (in press). (2000)

[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-a and -b Messenger RNA Expression in Human Breast Cancers by Real-time Polymerase Chain Reaction."Cancer. (in press). (2000)

[Publications] Miyoshi,Y., et al.: "Genetic Polymorphism in CYP17 and Breast Cancer Risk in Japanese Women."Eur J Cancer. (in press). (2000)

[Publications] Miyoshi,Y., et al.: "Association of Centrosomal Kinase STK15/BTAK mRNA Expression with Chromosomal Instability in Human Breast Cancers."Int J Cancer. (in press). (2000)

[Publications] Tsukamoto,F., et al.: "Clinicopathological Analysis of Breast Cancers with Chromosomal Aneusomy Detected by Fluorescence In Situ Hybridization."Cancer Cytopathol. (in press).

[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability of BRCA1-Associated Hereditary Breast Cancers by p53 Abnormality."Breast Journal. (in press).

野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)