EXPLOITATION OF NEW DIAGNO-THERAPEUTIC PROCEDURES OF HUMAN UTERINE ENDOCERVICAL AND ENDOMETRIAL ADENOCARCINOMAS BASED ON CYTOGENETIC STUDY OF MULTI- STEP CARCINOGENESIS

• Project/Area Number: 14571599
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: HIRAI Yasuo JAPANESE FOUNDATION FOR CANCER RESEARCH, CANCER INSTITUTE, RESEARCH FELLOW, 癌研究所・細胞生物部, 研究員 (00260076)
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: ENDOCERVICAL ADENOCARCINOMAS / ENDOMETRIAL ADENOCARCINOMA / GLASSY CELL CARCINOMA / CONVENTIONAL CGH / ARRAY-BASED CGH / MICROSATELLITE INSTABILITY / PTEN / HPV INFECTION / 子宮頸部腺癌 / HPV感染 / TCFβ typeII Receptor / TCF βtype II Recetpor

Research Abstract

We analyzed the mutational status of the TGF βRII, BAX, and PTEN/MMAC1 genes as well as microsatellite instability (MI) in consecutive cases of endocervical and endometrial adenocarcinomas of the uterus operated on at our Institute. To examine copy number losses and/or amplifications at the chromosomal region bearing all the genes, we used comparative genomic hybridization (CGH) analysis (both conventional and array-based). CGH analysis provides a genome-wide overview about tumor-associated genomic imbalances. Among the tumors, a few showed the MI+ phenotype in endocervical adenocarcinoma. Also, few tumors demonstrated a significant mutation with a definite amino acid change in PTEN/MMAC1 gene, which is prominent in endometrial adenocarcinoma. CGH analysis demonstrated several promising oncogenes which may have a role in multi-step carcinogenesis of uterine endocervical and endometrial adenocarcinomas.
Additional explorations are needed to elucidate the cytogenetic mechanisms of multi- step carcinogenesis in endocervical and endometrial adenocarcinomas of the uterus.

Research Products

• [Journal Article] Putative gene loci associated with carciongenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH (2004)
  • Author(s): Hirai Y
  • Journal Title: Am J Obstet Gynecol 191 Pages: 1173-1173
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phase II trial of 3-h infusion of paclitaxel in patients with adenocarcinoma of endometrium : Japanese Multicenter Study Group (2004)
  • Author(s): Hirai Y
  • Journal Title: Gynecol Oncol 94 Pages: 471-471
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Conventional and array-based comparative genomic hybridization analyses of novel cell lines harboring HPV18 from glassy cell carcinoma of the uterine (2004)
  • Author(s): Hirai Y
  • Journal Title: Int J Oncol 24 Pages: 977-977
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Putative gene loci associated with carcinogenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH. (2004)
  • Author(s): Hirai Y, Utsugi K, Takeshima N, Kawamata Y, Furuta R, Kitagawa T, Kawaguchi T, Hasumi K, Noda T.
  • Journal Title: Am J Obstet Gynecol., Erratum in : Am J Obstet Gynecol. Noda, Shirahama Tetsuo [corrected to Noda, Tetsuo]. Oct;191(4), Apr;192(4)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Phase II trial of 3-h infusion of paclitaxel in patients with adenocarcinoma of endometrium : Japanese Multicenter Study Group. (2004)
  • Author(s): Hirai Y, Hasumi K, Onose R, Kuramoto H, Kuzuya K, Hatae M, Ochiai K, Nozawa S, Noda K.
  • Journal Title: Gynecol Oncol. Aug;94(2) Pages: 471-476
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Conventional and array-based comparative genomic hybridization analyzes of novel cell lines harboring HPV18 from glassy cell carcinoma of the uterine cervix. (2004)
  • Author(s): Hirai Y, Kawamata Y, Takeshima N, Furuta R, Kitagawa T, Kawaguchi T, Hasumi K, Sugai S, Noda T.
  • Journal Title: Int J Oncol. Apr;24(4) Pages: 977-986
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Putative gene loci associated with carcinogenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH (2004)
  • Author(s): Hirai Y
  • Journal Title: Am J Obstet Gynecol 191 Pages: 1173-1173
• [Journal Article] A large-scale gene expression comparison of microdissected, small-sized endometrial cancers with or without hyperplasia matched to same-patent (2003)
  • Author(s): Sugiyama Y, Hirai Y
  • Journal Title: Clin Cancer Res 15 Pages: 5589-5589
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A large-scale gene expression comparison of microdissected, small-sized endometrial cancers with or without hyperplasia matched to same-patient normal tissue. (2003)
  • Author(s): Sugiyama Y, Dan S, Yoshida Y, Akiyama F, Sugiyama K, Hirai Y, Matsuura M, Miyata S, Ushijima M, Hasumi K, Yamori T.
  • Journal Title: Clin Cancer Res. Nov15:9(15) Pages: 5589-5600
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A large-scale gene expression comparison of microdissected, small-sized endometrial cancers with or without hyperplasia matched same-patient (2003)
  • Author(s): Sugiyama Y, Hirai Y
  • Journal Title: Clin Cancer Res 15 Pages: 5589-5589
• [Publications] Hirai Y, Takeshima N, et al.: "Early invasive cervical adenocarcinoma : its potential for nodal metastasis or recurrence"BJOG. 110. 241-246 (2003)
• [Publications] Hirai Y, Kawamata Y, et al.: "Conventional and array-based comparative genornic hybridization analyses of novel cell lines harboring HPV 18 from glassy cell carcinoma of the uterine cervix."Int J Oncol.. 24. 977-986 (2004)
• [Publications] Sugiyama Y, Hirai Y, et al.: "A large-scale gene expression comparison of microdissected, small-sized endometrial cancers with or without hyperplasia matched to same-patient normal tissue."Clin Cancer Res.. 15. 5589-5600 (2003)
• [Publications] Furuta R, Hirai Y, et al.: "Ectopic chromosome around centrosome in metaphase cells as a marker of high-risk human papillomavirus-associated cervical intraepithelial neoplasias."Int J Cancer.. 106. 167-171 (2003)
• [Publications] Tabata T, Hirai Y, et al.: "A randomized study or primary bleomycin, vincristine, mitornycin and cisplatin(BOMP) chemotherapy followed by radiotherapy versus radiotherapy alone in stage IIIB and IVA squamous cell carcinoma of the cervix."Anticancer Res.. 23. 2885-2890 (2003)
• [Publications] Yokoyama M, Hirai Y, et al.: "Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia : a cohort study in Japan."Cancer Lett.. 192. 171-179 (2003)
• [Publications] Hirai Y, Takeshima N, et al.: "Early invasive cervical adenocarcinoma : its potential for nodal metastasis or recurrence"BJOG. 110. 241-246 (2003)
• [Publications] Kawana K, Hiral Y, et al.: "Neutralizing antibodies against oncogenic human papillomavirus as a possible determinant of the fate of low-grade cervical intraepithelial neoplasia"Biochem Biophys Res Commun. 296. 102-105 (2002)
• [Publications] Zheng K, Hirai Y, et al.: "A Quantitative Evaluation of Active Gelatinolytic Sites in Uterine Endometrioid Adenocarcinoma Using Film in situ Zymography"Jpn J Cancer Res. 93. 516-522 (2002)
• [Publications] Tabata T, Hirai Y, et al.: "Treatment failure in vaginal cancer"Gynecol Oncol. 84. 309-314 (2002)
• [Publications] Sugiyama Y, Hirai Y, et al.: "Microdissection is essential for gene expression profiling of clinically resected cancer tissues"J Clin Pathol. 117. 109-116 (2002)