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Molecular biologic prognostic factors in soft tissue sarcomas

Research Project

Project/Area Number 12670167
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

ODA Yoshinao  Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究院, 講師 (70291515)

Co-Investigator(Kenkyū-buntansha) TAMIYA Sadafumi  School of Health Sciences, Associate Professor, 医学部, 助教授 (60284486)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsSoft tissue sarcoma / p53 / MDM2 / H-ras / Prognosis / Synovial sarcoma / beta-catenin / Malignant peripheral nerve sheath tumor / 悪性軟部腫瘍 / 平滑筋肉腫 / PTEN / MMAC1 / 胞巣状軟部肉腫 / DNAミスマッチ修復遺伝子 / hMLH1 / hMSH2 / 悪性線維性組織球種 / 多形型平滑筋肉腫 / 皮膚異型繊維性黄色腫 / 炎症性筋線維芽細胞性腫瘍 / P53 / YB-1 / 軟部悪性腫傷 / 予後 / DNA / mutation
Research Abstract

We have carried out extensive investigations into the molecular biologic characteristics of several kinds of soft-tissue sarcomas and the following results have been obtained.
1. Dedifferentiated liposarcoma or chondrosarcoma: The frequency of p53 gene alterations and H-ras gene alteration in dedifferentiated component was higher than those in well differentiated component within the same tumor.
2. Synovial sarcoma: The detection of SYT-SSX fusion transcripts is a useful diagnostic tool in this tumor, however, its subtype has no correlation with patient's prognosis. An increased rate of apoptosis, a low p27/kip1-labeling index, reduced expression of E-cadherin and alpha-catenin, aberrant expression of beta-catenin, beta-catenin gene mutation, and co-expression of hepatocyte growth factor (HGF) and c-MET are all adverse prognostic factors. E-cadherin gene alteration has no correlation with prognosis, however, it is one of the causes of epithelial-mesenchymal transition in this tumor. Molecular abnormalities of p53, MDM2 and ras gene have no correlation with prognosis.
3. Malignant rhabdoid tumor (MRT):
p53 gene alterations occur frequently. All examined cases showed hSNF5/INI1 gene alterations.
4. Malignant peripheral nerve sheath tumor (MPNST): The expression of p53 protein, TGF- beta 1, TGF-beta receptor type II, HGF and c-MET is higher in the areas of MPNST than in the neurofibromatous areas within the same tumor in patients with von Recklinghausen's disease. High MIB-1 labeling index and the presence of rhabdomyoblasts (Malignant Triton tumor) were adverse prognostic factors in MPNST. The alteration of p53 did not affect the patients survival.
5. Sporadic desmoid tumor: Beta-catenin accumulation has a significant relationship with cyclin D1 overexpression. In a beta-catenin mutated group, cyclin D1 mRNA expression was found to be significantly higher than that in a beta-catenin wild-type group.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Oda Y et al.: "Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma"Human Pathology. 31. 185-192 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oda Y et al.: "Molecular abnormalities of p53, MDM2 and H-ras in synovial sarcoma"Modern Pathology. 13. 994-1004 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y et al.: "Prognostic value of the preserved expressions of adhesion molecules (E-cadherin and catenin families) and beta-catenin mutation in synovial sarcoma"Journal of Pathology. 342. 342-350 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakamoto A, Oda Y et al.: "H-ras oncogene mutations in dedifferentiated liposarcomas. PCR-RFLP analysis of paraffin-embedded tissues"American Journal of Clinical Pathology. 115. 235-242 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe T, Oda Y et al.: "Malignant peripheral nerve sheath tumors : high Ki67 labelling index is the significant prognostic indicator"Histopathology. 39. 187-197 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y et al.: "Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in soradic desmoid tumors : Real-time semiquantative assay by TaqMan PCR"Laboratory Investigation. 82. 97-103 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawauchi S, Fukuda T, Oda Y, Saito T, Oga A, Takeshita M, Yokoyama K, Chuman H, Iwamoto Y, Sasaki K, Tsuneyoshi M: "Correlation with clinicopathologic parameters, cell proliferative activity and expression of apoptosis-related proteins"Mod Pathol.. 13. 755-765 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kinoshita K, Shiratsuchi H, Tamiya S, Oshiro Y, Oda Y, Suita S, Tsuneyoshi M: "Establishment and characterization of malignant rhabdoid tumor of the kidney : Immunohistochemical and cytogenetical analysis"Oncology Reports. 8. 43-48 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kinoshita Y, Shiratsuchi H, Tamiya S, Oshiro Y, Oda Y, Suita S, Tsuneyoshi M: "Mutations of p53 fene in malignant rhabdoid tumors of soft tissue and kidney ; Immunohistochemical and DNA direct wequence analysis"J Cancer Res Clin Oncol.. 127. 351-358 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakamoto A, Oda Y, Adachi T, Oshiro Y, Tamiya S, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M: "H-ras oncogene mutation in dedifferentiated chondrosarcoma : Polymerase chain reaction-restriction fragment length polymorphism analysis"Mod Pathol.. 14. 343-349 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe T, Oda Y, Tamiya S, Masuda K, Tsuneyoshi M: "Malignant peripheral nerve sheath tumour arising within neurofibroma. An immunohistochemical analysis in the comparison between benign and malignant components."J Clin Pathol.. 54. 631-636 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y, Tanaka K, Matsuda S, Tamiya S, Iwamoto Y, Tsuneyoshi M: "Beta-catenin nuclear expression correlates with cyclin D1 overexpression in sporadic desmoid tumors"J Pathol.. 195. 222-228 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y, Sugimachi K, Kawaguchi K, Tamiya S, Tanaka K, Matsuda S, Sakamoto A, Iwamoto Y, Tsuneyoshi M: "E-Cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features"Am J Pathol.. 159. 2117-2124 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oda Y, Sakamoto A, Saito T, Iwamoto Y, Kinukawa N, Tsuneyoshi M: "Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma"Hum. Pathol.. 31. 185-192 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawauchi S, Fukuda T, Oda Y, Saito T, Oga A, Takeshima M, Yokoyama K, Chuman H, Iwamoto Y, Sasaki K, Tsuneyoshi M: "Prognostic significance of apoptosis in synovial sarcoma: Correlation with clinicopathologic parameters, cell proliferative activity and expression of apoptosis-related proteins"Mod Pathol. 13. 755-765 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oda Y, Sakamoto A, Saito T, Kawauchi S, Iwamoto Y, Tsuneyoshi M: "Molecular abnormalities of p53, MDM2 and H-ras in synovial sarcoma"Mod Pathol. 13. 994-1004 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y, Sakamoto A, Tamiya S, Kinukawa N, Hayashi K, Iwamoto Y, Tsuneyoshi M: "Prognostic value of the preserved expressions of adhesion molecules (E-cadherin and catenin families) and beta-catenin mutation in synovial sarcoma"J Pathol. 192. 342-350 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kinoshita K, Tamiya S, Oda Y, Hirano K, Mimori K, Inoue H, Ohta S, Suita S, Tsuneyoshi M: "Establishment and characterization of malignant rhabdoid tumor of the kidney: Immunohistochemical and cytogenetical analysis"Oncology Reports. 8. 43-48 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kinoshita Y, Shiratsuchi H, Tamiya S, Oshiro Y, Oda Y, Suita S, Tsuneyoshi M: "Mutations of p53 gene in malignant rhabdoid tumors of soft tissue and kidney: Immunohistochemical and DNA direct sequence analysis"J Cancer Res Clin Oncol. 127. 351-358 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakamoto A, Oda Y, Adachi T, Tamiya S, Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M: "H-ras oncogene mutations in dedifferentiated liposarcomas. Polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues"Am J Clin Pathol. 115. 235-242 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakamoto A, Oda Y, Adachi T, Oshiro Y, Tamiya S, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M: "H-ras oncogene mutation in dedifferentiated chondrosarcoma: Polymerase chain reaction-restriction fragment length polymorphism analysis"Mod Pathol. 14. 343-349 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe T, Oda Y, Tamiya S, Masuda K, Tsuneyoshi M: "Malignant peripheral nerve sheath tumor arising within neurofibroma. An immunohistochemical analysis in the comparison between benign and malignant components"J Clin Pathol. 54. 631-636 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y, Tanaka K, Matsuda S, Tamiya S, Iwamoto Y, Tsuneyoshi M: "Beta-catenin nuclear expression correlates with cyclin D1 overexpression in sporadic desmoid tumors"J Pathol. 195. 222-228 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe T, Oda Y, Tamiya S, Kinukawa N, Masuda K, Tsuneyoshi M: "Malignant peripheral nerve sheath tumors: high Ki67 labeling index is the significant prognostic indicator"Histopathology. 39. 187-197 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y, Sugimachi K, Kawaguchi K, Tamiya S, Tanaka K, Matsuda S, Sakamoto A, Iwamoto Y, Tsuneyoshi M: "E-Cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features"Am J Pathol. 159. 2117-2124 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Oda Y, Kawaguchi K, Tanaka K, Matsuda S, Tamiya S, Iwamoto Y, Tsuneyoshi M: "Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in soradic desmoid tumors: Real-time semiquantative assay by TaqMan PCR"Lab Invest. 82. 97-103 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oda Y et al.: "Reassessment of malignant fibrous histiocytoma of soft parts and its clinicopathologic prognostic factors"Pathology International. 52. 595-606 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oda Y et al.: "Nuclear expression of Y box-binding protein-1 correlates with P-glycoprotein and topoisomerase II-apha expression, and poor prognosis in synovial sarcoma"Journal of Pathology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito T et al.: "PTEN/MMAC1 gene mutationis a rare event in soft tissue sarcomas without specific balanced translocations"International Journal of Cancer. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakamoto A et al.: "Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated liposarcoma and malignant fibrous histiocytoma"Arch Pathol Lab Med. 126. 1071-1078 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oda Y et al.: "Molecular genetic abnormalities and their usefulness for diagnosis and prediction of prognosis in soft-tissue sarcomas"Recent Res Devel Cancer. 4. 305-315 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito T et al.: "APC mutations in synovial sarcoma"Journal of Pathology. 196. 445-449 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazima K et al.: "Novel approach to P53 and MDM2 status in leiomyosarcoma Real-time semi-duantative RT-PCR"Cancer Letters. 164. 177-188 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Adachi T et al.: "Expression of P53, MDM2, and P21/WAF1 in dedifferentiated liposarcomas"Int. J. Surg. Pathol.. 9. 99-109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawauchi S et al.: "Low expression of P27, a cyclin-dependent kinase inhibitor, is a marker of poor proghosis in synorial sarcoma"Cancer. 91. 1005-1012 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanabe T et al.: "Malignant peripheral nerve sheath tumors : high ki67 labelling index is the significant prognostic indicator"Histopathology. 39. 187-197 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Oda Y et al.: "Pleomorphic leiomyosarcoma :"Am. J. Surg. Pathol.. 25. 1030-1038 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakamoto A et al.: "H-, K-, and N-ras mutation in atypical tibroxanthoma and malignant tibrous histiocytoma"Hum. Pathol.. 32. 1225-1231 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matanebe T et al.: "H-ras-1 point mutation in malignant pavipheval nerve sheath tumors,PCR-RFLP analysis and direct sequencing from paraffin embedded tissues."International Journal of Molecular Medicine. 5. 605-608 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oda Y et al.: "Molecular abhormalities of p53, MDM2, and H-ras in synovial sarcoma"Modern Pathology. 13. 994-1004 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinoshita Y et al.: "P53 gene mutations in malignant rhabdoid tumors of soft part and kidney"Journal of Cancer Research and Clinical Oncology. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakamtot A et al.: "H-ras oncogene mutations in dedifferentiated liposarcomas."American Journal Clinical Pathology. (in press).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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