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2001 Fiscal Year Final Research Report Summary

Clinical Application of Genetic Diagnosis of Breast Cancer

Research Project

Project/Area Number 11307019
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionOsaka University

Principal Investigator

NOGUCHI Shinzaburo  Osaka University, Surgical Oncology, Professor, 医学系研究科, 教授 (10303942)

Co-Investigator(Kenkyū-buntansha) TANJI Yoshio  Osaka University, Surgical Oncology, Research Associate, 医学系研究科, 助手 (90263269)
TAGUCHI Tetsuya  Osaka University, Surgical Oncology, Lecturer, 医学系研究科, 講師 (80243260)
TAMAKI Yasuhiro  Osaka University, Surgical Oncology, Associate Professor, 医学系研究科, 助教授 (10273690)
TSUKAMOTO Fumine  Osaka University, Surgical Oncology, Research Associate, 医学系研究科, 助手 (70303964)
MIYOSHI Yasuo  Osaka University, Surgical Oncology, Research Associate, 医学系研究科, 助手 (50283784)
Project Period (FY) 1999 – 2001
KeywordsBreast cancer / Genetic diagnosis / Nucrinetastasis / BRCA1 / BRCA2 / Risk assessment / BRCA2
Research Abstract

Summary of our research intended for clinical application of genetic diagnosis of breast cancer is described below : (1) Differential diagnosis of benign and malignant breast tumors by FISH : FISH diagnosis of fine needle aspiration biopsy samples from breast tumors has a diagnostic accuracy comparable to conventional cytology and is useful in making a definitive deagnosis of malignancy in cases with indeterminate and benign cytological results. (2) Diagnosis of prognosis : Bone marrow micrometastases detected by a real-time RT-PCR assay of CK19 or mammaglobin mRNA can serve as a significant prognostic factor being independent of the other conventional prognostic factors. In addition, we have also found that high expression of BRCA2 mRNA or wt-1 mRNA in tumor rtissues is significantly associated with poor prognosis. (3) Genetic diagnosis of familial breast cancer : Fifteen BRCA1 (13.3%) and 21 BRCA2 (18.6%) mutations were identified in 113 Japanese breast cancer families. BRCA1 associated-tumors have been found to have biologically aggressive phenotypes and to show a poorer prognosis as compared with sporadic breast tumors. (4) Genetic polymorphism and breast cancer risk : A significant increase in breast cancer risk (odds ratio = 1.56, P = 0.028) was observed in CYP17^<1931C/C> homozygotes as compared with CYP17^<1931T/C> heterozygotes and CYP17^<1931T/T> homozygotes. Homozygous carriers of the allele with 10 or more TTTA repeats at intron 4 of CYP19 showed a trend toward an increase (OR = 1.80, 95%C.i. = 0.97-3.36) in breast cancer risk.

  • Research Products

    (68 results)

All Other

All Publications (68 results)

  • [Publications] Noguchi, S. et al.: "Clinicopathological analysis of BRCA1-or BRCA2-associated hereditary breast carcinoma in Japanese women"Cancer. 85. 2200-2205 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshikawa K. et al.: "Reduction of BRCA1 protein expression in Japangse sporadic breast carcinomas and its frequent loss in BRCA1-associated cases"Clin. Cancer Res. 5. 1249-1261 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motomura, K. et al.: "Sentinel node biopsy guided by indocyanine green dye in breast cancer patients"Jpn. J Clin. Oncol. 29. 604-607 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motomura, K. et al.: "Malignant seeding of the lumpectomy cavity upon breast-conserving surgery"Oncology. 57. 121-126 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motomura, K. et al.: "Sentinel node biopsy in breast cancer patients with clinically negative lymph-nodes"Breast cancer. 6. 259-262 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Breast cancer Risk associated with polymorphism in CYP19 in Japanese women"Int. J Cancer. 89. 325-328 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Acceleration of chromosomal instability by loss of BRCA1 expression and p53 abnormality in sporadic breast cancers"Cancer Lett. 159. 211-216 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [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. 90. 373-378 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda N. et al.: "Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families"Int. J Cancer. 91. 83-88 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim, SJ. et al.: "Detection of breast cancer micrometastases in peripheral blood using immunomagnetic separation and immunocytochemistry"Breast Cancer. 8. 63-69 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao K. et al.: "Quantitative analysis of estrogen receptor-β messenger RNA and its variants in human breast cancers"Int. J Cancer. 88. 733-736 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao K. et al.: "Quantitative analysis of estrogen receptor-α and β messenger RNA expression in human breast by real-time polymerase chain reaction"Cancer. 89. 1732-1738 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Genetic polymorphism in CYP17 and breast cancer risk in Japanese Women"Eur J Cancer. 36. 2375-2379 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers"Int. J Cancer. 92. 370-373 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukamoto, F. et al.: "Clinicopathological analysis of breast cancers with chromosomal aneusomy detected by fluorescence In situ hybridization"Cancer. 93. 165-170 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motomura, K. et al.: "Combination techiniqne is superior to dye alone in identification of the sentinel node in breast cancer patients"J Surg. Oncol. 76. 96-99 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Egawa, C. et al.: "Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characteristics"Jpn. J Cancer Res.. 92. 624-630 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Egawa, C. et al.: "Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancers"Int J Cancer. 95. 255-259 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takamura, Y. et al.: "Prediction of chemotherapentic response by technetium-99m-MIBI scintigraphy in breast cancer patients"Cancer. 92. 232-239 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motomura, K. et al.: "Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients"Enr. J Surg. Oncol. 27. 141-145 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takami S. et al.: "Chromosomal instability detected by flurescence in situ hybridization in Japanese breast cancer patients"Clin. Chim. Acta. 308. 127-131 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao K. et al.: "Quantitative analysis of estrogen receptor-alpha and-beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction"Cencer Lett.. 170. 91-97 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ooka, M. et al.: "Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer"Breast Cancer Res. Treat. 67. 169-175 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Clinicopathological characteristics of estrogen receptor-beta positive human breast cancers"Jpn. J Cancer Res.. 92. 1057-1061 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Prediction of response to docetaxel by CYP3A4 mRNA expregsion in breast cancer"Int. J Cancer. 97. 129-132 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Egawa, C. et al.: "Quantitative Analysis of Estrogen Receptor-alpha and-beta Messenger RNA Expression in Normal and Malignant Thyroid Tissues by Real-time Polymerase Chain Reaction"Oncology. 61. 293-298 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Involvement of 17beta-Hydroxysteroid behtdrogease up-regulation in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers"Int. J Cancer. 94. 685-689 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takamura, Y. et al.: "Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers"Int. J Cancer. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Egawa, C. et al.: "High BRCA2 mRNA expressio predicts poor prognosis in breast cancer patients"Int. J Cancer. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimazu K. et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentimel lymph node biopsy in breast cancer patients"Surgery,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women"Breast Journal. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyoshi, Y. et al.: "Acceleration of chromosomal instability of BRCA1-associated hereditary breast cancers by p53 abnormality"Breast Journal. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwao K. et al.: "Molecular classification of primary breast tumors possessing distinct prognostic properties"Hum Mol Genet.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noguchi, S., et al.: "Clinicopathological analysis of BRCA1- or BRCA2-associated hereditary breast carcinoma in Japanese women"Cancer. 85. 2200-2205 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshikawa, K., et al.: "Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases"Clin Cancer Res.. 5. 1249-1261 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motomura, K., et al.: "Sentinel node biopsy guided by indocyanine green dye in breast cancer patients"Jpn J. Clin Oncol. 29. 604-607 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motomura, K., et al.: "Malignant seeding of the lumpectomy cavity upon breast-conserving surgery"Oncology. 57. 121-126 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motomura, K., et al.: "Sentinel node biopsy in breast cancer Pptients with clinically negative lymph-nodes"Breast Cancer. 6. 259-262 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi, Y., et al.: "Breast cancerrRisk associated with polymorphism.in CYP19 in Japanese women"Int J Cancer. 89. 325-328 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi, Y., et al.: "Acceleration of chromosomal instability by loss of BRCA1 expression and p53 abnormality in sporadic breast cancers"Cancer Lett. 159. 211-216 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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. 90. 373-378 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda, N., et al.: "Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families"Int J Cancer. 91. 83-88 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kim, SJ., et al.: "Detection of breast cancer micrometastases in peripheral blood using immunomagnetic separation and immunocytochemistry"Breast Cancer. 8. 63-69 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao, K., et al.: "Quantitative analysis of estrogen receptor-β messenger RNA and its variants in human breast cancers"Int J Cancer. 88. 733-736 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao, K., et al.: "Quantitative analysis of estrogen receptor-α and -βmessenger RNA expression in human breast cancers by real-time polymerase chain reaction"cancers. 89. 1732-1738 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi, Y., et al.: "Genetic polymorphism in CYP17 and Breast cancer risk in Japanese Women"Eur J Cancer. 36. 2375-2379 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi,: Y., et al.: "Assciation pf centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers"Int J Cancer. 92. 370-373 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukamoto, F., et al.: "Clinicopathological analysis of breast cancers with chromosomal aneusomy detected by fluorescence In situ hybridization"Cancer. 93. 165-170 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motomura, K., et al.: "Combination techinique is superior to dye alone in identification of the sentinel dode in breast cancer patients"J Surg Oncol. 76. 96-99 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Egawa, C., et al.: "Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas arid its relationship with clinicopathlogical characteristics"Jpn J Cancer Res.. 92. 624-630 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Egawa, C., et al: "Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancers"Int J Cancer. 95. 255-259 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takamura, Y., et al.: "Prediction of chemotherapeutic response by technetium-99m-MIBI scintigraphy in breast cancer patients"Cancer. 92. 232-239 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motomura, K., et al.: "Gamma probe arid ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients"Eur J Surg Oncol. 27. 141-145 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takami, S., et al.: "Chromosomal instability detected by fluorescence in situ hybridization in Japanese breast cancer patients"Clin Chim Acta. 308. 127-131 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao, K., et al.: "Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction"Cancer Lett.. 170. 91-97 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ooka, M., et al.: "Breast Cancer Res Treat, Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer"67. 169-175 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] MIyoshi, Y., et al.: "Clinicopathological characteristics of estrogen receptor-beta positive human breast cancers"Jpn J Cancer Res. 92. 1057-1061 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi, Y., et al.: "Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer"Int J Cancer. 97. 129-132 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Egawa, C., et al.: "Quantitative Analysis of Estrogen Receptor-alpha and -beta Messenger RNA Expression in normal and Malignant Thyroid Tissues by Real-time Polymerase Chain Reaction"Oncology. 61. 293-298 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi, Y. et al.: "Involvement of 17beta-Hydroxysteroid dehydrogenase up-regulation in maintenance of intratumoral high estradiol levels in Postmenopausal breast cancers"Int J Cancer. 94. 685-689 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takamura, Y., et al.: "Prediction of chemotherapeutic response by collagen gel droplet embedded culture- drug sensitivity test in human breast cancers"Int J Cancer. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Egawa, C., et. al.: "High BRCA2 mRNA expression Predicts Poor Prognosis in breast cancer patients"Int J Cancer. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, K., et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentinel lymph node biopsy in breast cancer patients"Surgery. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyoshi, Y., et al.: "Breast Cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women"Breast Journal. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] MIyoshi, Y., et al.: "Acceleration of chromosomal instability of BRCA1-associated hereditary breast cancers by p53 abnormality"Breast Journal. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwao, K., et al.: "Molecular classification of primary breast tumors opssessing distinct prognostic properties"Hum Mol Genet. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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