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Molecular-pathologic and clinicopathologic study on the heterogeneity of early development and progression of ovarian cancer

Research Project

Project/Area Number 07457608
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KONISHI Ikuo  Kyoto University, Gynecology and Obstetrics, Assistant Professor, 医学研究所, 講師 (90192062)

Co-Investigator(Kenkyū-buntansha) YAMABE Hirohiko  Kyoto University, Pathology, Associate Professor, 医学研究所, 助教授 (00135592)
SAGAWA Norimasa  Kyoto University, Gynecology and Obstetrics, Associate Professor, 医学研究所, 助教授 (00162321)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsovarian cancer / carcinogenesis / heterogeneity / p53 / K-ras / nm23 / VEGF / gonadotropin / 性ステロイド受容体
Research Abstract

Little is known about the early pathogenic process of ovarian carcinogenesis, because more than half of ovarian cancer patients are diagnosed at the advanced stages. Ovarian epithelial tumors originate from the surface epithelium covering the ovary, and there are three types with distinct clinicopathology ; benign cystadenoma, tumor of low malignant potential (LMP), and invasive carcinoma. However, it is unknown whether ovarian carcinomas occur de novo in the ovarian surface or develop as a result of the malignant transformation of benign or LMP tumors of the ovary. To address this issue, we studied the clinical course in detail of ovarian cancer development, and molecular pathologic analysis on heterogeneity of genetic alterations in ovarian tumors. In addition, we examined the expression of various genes with reference to the tumor progression.
Analysis of the clinical findings of ovarian cancer development in infertility patients revealed that serous carcinomas are frequently at the … More advanced stages when the tumor was first recognized, whereas endometrioid or clear cell carcinomas arising in endometriotic cyst are at the early stage. Expression of gonadotropin receptors in ovarian cancers and apoptosis-inhibitory effect of gonadotropins in ovarian cancer cells suggest that gonadotropins play an important role in ovarian carcinogenesis.
Immunohistochemical analysis of p53 protein expression in ovarian tumors showed that p53-positive tumor cells are homogeneously distributed in serous carcinomas, whereas heterogeneous in mucinous carcinomas. K-ras-mutated tumor cells are also heterogeneously present in accordance with histopathology. These findings suggest that serous carcinomas arise de novo in the ovarian surface, whereas mucinous carcinomas develop in the benign or LMP tumors.
Overexpression of C-erbB-2 gene and decreased expression of metastasis-related nm23 gene are both important for distant metastasis of ovarian carcinomas. However, nm23 gene mutation is rare in ovarian carcinomas. Overexpression of vascular endothelial growth factor (VEGF) may play an essential role in peritoneal involvement with ascites formation in ovarian carcinomas, and serum VEGF levels is a novel tumor marker in ovarian cancer patients. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Koshiyama, M., et al.: "Immunohistochemical analysis of p53 protein and 72 kDa heat shock protein (HSP72) expression in ovarian carcinomas : correlation with" Virchows Archiv. 425. 603-609 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mandai, M., et al.: "Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma : correlation with tumour" Brj Cancer. 72. 691-695 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Komatsu, T., et al.: "Peritoneal papillary serous carcinoma arising in an infertile woman during ovulation-induction therapy : immunohistochemical expression" Gynecol Oncol. 56. 470-474 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Konishi, I.: "Review : infertility therapy and ovarian carcer." Adv Obstet Gynecol. 48. 387-395 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Komatsu, T., et al: "Adnexal mass : comparison of transvaginal US and gadoliniumenhanced MR imaging assessment of intratumoral structure." Radiology. 198. 109-115 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mandai, M., et al.: "Messenger ribonucleic acid expresion of LH/hCG receptor gene in human ovarian carcinomas." Eur J Cancer. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 小西郁生,万代昌紀: "図説産婦人科VIEW分子細胞生物学("卵巣悪性腫瘍と癌遺伝子")" メジカルビュー社(印刷中), (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koshiyama, M., Konishi, L., et al.: "Immunohistochemical analysis of p53 protein and 72 kDa heat shock protein (HSP72) expression in ovarian carcinomas : correlation with clinicopathology and sex steroid receptor status." Virchows Archiv. 425. 603-609 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mandai, M., Konishi, I., et al.: "Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma : correlation with tumour progression and nm23 gene expession." Br J Cancer. 72. 691-695 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Komatsu, T., Konishi, I., et al.: "Peritoneal papillary serous carcinoma arising in an infertile woman during ovulaation-induction therapy : immunohistochemical expression of LH/hCG receptors." Gynecol Oncol. 56. 470-474 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Konishi, I.: "Review : infertility therapy and ovarian cancer." Adv Obstet Gynecol. 48. 387-395 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Komatsu, T., Konishi, I., et al.: "Adnexal mass : comparison of transvaginal US and gadolinium-enhanced MR imaging assessment of intratumoral structure." Radiology. 198. 109-115 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kobayashi, F., Konishi, I., et al.: "Rapid growth of ovarian clear cell carcinomas expressing LH/hCG receptor arising from endometriosis during early pregnancy." Gynecol Oncol. 62. 309-313 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mandai, M., Konishi, I., et al.: "Messenger ribonucleic acid expression of LH/hCG receptor gene in humaan ovarian carcinomas." Eur J Cancer. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Komatsu,T.,et al.: "Adnexal mass : comparison of transvaginal US and Gadolinium" Radiology. 198. 109-115 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mandai,M.,et al.: "Ascitic positive cytology and intraperitoneal metastasis" J.Obstet.Gynaecol.Res.22. 89-94 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kobayashi,F.,et al.: "Rapid growth of ovarian clear cell carcinoma expressing LH/hCG" Gynecol.Oncol.62. 309-313 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mandai,M.,et al.: "Messenger ribonucleic acid expression of LH/hCG receptor" Eur.J.Cancer. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小西郁生: "不妊症治療と卵巣癌" 産婦進歩. 48. 387-395 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 八木治彦ほか: "α-fetoprotein産生を示した卵巣類内膜癌の病理組織学的検討" 産婦進歩. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小西郁生、万代昌紀: "“卵巣悪性腫瘍と癌遺伝子"/図説産婦人科VIEW分子細胞生物学" メジカルビュー社(印刷中), (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Koshiyama, M., et al.: "Immunohistochemical analysis of p53 protein and 72KDa heat shock protein" Virchows Archiv. 425. 603-609 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Komatsu, T., et al.: "Pritoneal papillary serous carcinoma arising in an infertile woman" Gynecol Oncol. 56. 470-474 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mandai, M., et al.: "Altered expression of nm23-H1 and c-erbB-2 proteins have" Cancer. 75. 2523-2529 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mandai, M., et al.: "Mutation of the nm23 gene, loss of heter ozygosity at the nm23" Br. J. Cancer. 72. 691-695 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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