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Re-classification of pancreatobiliary tumors by mucin expression profile - An application to the operative indication -

Research Project

Project/Area Number 12470046
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKagoshima University

Principal Investigator

YONEZAWA Suguru  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10175002)

Co-Investigator(Kenkyū-buntansha) TSUYAMA hinichiro  Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (30041346)
TAKAO Sonshin  Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80171411)
AIKOU Takashi  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (60117471)
NOMOTO Mitsuharu  Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (20274813)
GOTO Masamichi  Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80325779)
松下 能文  鹿児島大学, 医学部, 助手 (90244227)
東 美智代  鹿児島大学, 医学部, 助手 (60315405)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordspancreatobiliary tumor / mucin / immunohistochemistry / clinicopathological factor / prognosis of patient with cancer / operative indication / DNA methylation / microdissection / 膵腫瘍 / 胆管腫瘍 / 膵管内乳頭腫瘍 / 肝内胆管癌 / 肝外胆管癌 / MUC1ムチン / MUC2ムチン / 分子病理学 / 組織型 / 分子病理学的
Research Abstract

We examined the expression profiles of membrane mucins (MUC1 and MUC4) and secretory mucins (MUC2, MUC5AC and MUC6) hi many pancreatobiliary tumors, and compared the results with clinicopathological factors of the patients with those tumors.
In pancreatic tumors, we examined mucins expression in invasive ductal carcinomas (IDCs) and intraductal papillary mucinous neoplasms (IPMNs) using immunohistochemistry and in situ hybridization. IPMNs were classified into two histological subtypes, "dark cell type (IPM N-D" and "clear cell type (IPMN-C). IDCs showed high expression of all the glycoforms of MUC1. IPMNs-D showed no or low expression of all the glycoforms of MUC1. IPMNs-C showed low expression of poorly glycosylated MUC1 (MUC1/DF3), but expression of glycosylated MUC1 (MUC1/HMFG-1). Expression of MUC2 was negative in IDC, high in IPMN-D and low in IPMN-C. MUC5AC was highly expressed in all the types. MUC6 expression was higher in IPMNs-C than in IDCs and IPMNs-D.
In intrahepatic cholan … More giocarcinoma-mass forming type, MUC4 expression was a statistically significant independent risk factor. Mucin-producing bile duct tumors were classified into two distinct categories by the histopathological findings, morphometry and mucin expression profiles, and there was a significant difference of the survivals between the two patient groups with two different tumors. In the patients with extrahepatic bile duct carcinomas, MUC1/DF3 was the most useful prognosis indicator among the various glycoforms of MUC1 mucins. For the comparative studies with the pancreatobiliary tumors, we also studied expression profiles of mucins in the tumors of other organs such as colon, breast, etc.
To investigate the expression mechanism of MUC2 in the tumors, we examined DNA methylation in promotor areas of MUC2 gene in pancreatic carcinoma cells with MUC2 + or - expression, using methylation specific PCR. The promotor area of MUC2 gene was unmethylated in pancreatic carcinoma calls with MUC2 + expression, whereas it was methylated in pancreatic carcinoma cells with MUC2 - expression. Expression mechanism of MUC2 in the pancreatic tumors may be regulated by DNA methylation in the promptor areas of MUC2 gene. We also could amplify DNA from a small amount of tissues obtained by microdissection. Less

Report

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

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Wu, X., et al.: "Expression of mucin 1 (MUC1) in benign, premalignant and malignant vulvar tumors"Acta Histochem. Cytochem.. 33・4. 267-273 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, A., et al.: "Expression of MUC1 and MUC2 mucins and relationship with cell proliferative activity in human colorectal neoplasia"Pathol. Int.. 51・11. 853-860 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wang, F., et al.: "Altered GalNAc-α-2,6-sialylation compartments for mucin-associated sialyl-Tn antigen in colorectal adenoma and adenocarcinoma"J. Histochem. Cytochem.. 49・12. 1581-1591 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, A., et al.: "Comparative study for histology, proliferative activity, glycoproteins, and p53 protein between old and recent colorectal adenomas in Japan"Cancer Lett.. 170・1. 45-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 米澤 傑, 他: "ムチンの発現様式から見た通常型膵管癌の組織発生 -膵管内乳頭腫瘍との対比 -"胆と膵. 23・3. 187-194 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamada, S., et al.: "Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas : Its relationship with tumor progression and prognosis"Pathol. Int.. 52・11. 713-723 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seko, A., et al.: "Ectopic expression of a GlcNAc 6-O-sulfotransferase, GlcNAc6ST-2, in colonic mucinous adenocarcinoma"Glycobiology. 12・6. 379-388 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yonezawa, S., et al.: "The expression of several types of mucin is related to the biological behavior of pancreatic neoplasms"J. Hepatobiliary Pancreat. Surg.. 9・3. 328-341 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seko, A., et al.: "Down-regulation of Gal 3-O-sulfotransferase-2 (Gal3ST-2) expression in human colonic non-mucinous adenocarcinoma"Jpn. J. Cancer Res.. 93・5. 507-515 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshii, N., et al.: "Expression of mucin core proteins in extramammary Paget's disease"Pathol. Int.. 52・5/6. 390-399 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, A., et al.: "New classification of pancreatic intraductal papillary-mucinous tumour by mucin expression : its relationship with potential for malignancy"J. Pathol.. 197・2. 201-210 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsukita, S., et al.: "Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast : comparison with invasive ductal carcinoma"Histopathology. 42・1. 26-36 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wu, X., et al.: "Expression of mucin 1 (MUC1) in benign, premalignant and malignant vulvar tumors"Acta Histochem. Cytochem.. 33(4). 267-273 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, A, et al.: "Expression of MUC1 and MUC2 mucins and relationship with cell proliferative activity in human colorectal neoplasia"Pathol. Int.. 51(11). 853-860 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wang, F., et al.: "Altered GalNAc-α-2, 6-sialylation compartments for mucin-associated sialyl-Tn antigen in colorectal adenoma and adenocarcinoma"J. Histochem. Cytochem.. 49(12). 1581-1591 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, A., et al.: "Comparative study for histology, proliferative activity, glycoproteins, and p53 protein between old and recent colorectal adenomas in Japan"Cancer Lett.. 170(1). 45-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yonezawa, S., et al.: "Histogenesis of common-type invasive ductal carcinoma from a viewpoint of mucin expression pattern - comparison with intraductal papillary mucinous neoplasm"Tan to Sui (in Japanese). 23(3). 187-194 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamada, S., et al.: "Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas : Its relationship with tumor progression and prognosis"Pathol. Int.. 52(11). 713-723 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seko, A, et al.: "Ectopic expression of a GlcNAc 6-O-sulfotransferase, GlcNAc6ST-2, in colonic mucinous adenocarcinoma"Glycobiology. 12(6). 379-388 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yonezawa, S., et al.: "The expression of several types of mucin is related to the biological behavior of pancreatic neoplasms"J. Hepatobiliary Pancreat. Surg.. 9(3). 328-341 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seko, A., et al.: "Down-regulation of Gal 3-O-sulfotransferase-2 (Gal3ST-2) expression in human colonic non-mucinous adenocarcinoma"Jpn. J. Cancer Res.. 93(5). 507-515 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshii, N., et al.: "Expression of mucin core proteins extramammary Paget's disease"Pathol. Int.. 52(5/6). 390-399 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, A., et al.: "New classification of pancreatic intraductal papillary-mucinous tumor by mucin expression : its relationship with potential for malignancy"J. Pathol.. 197(2). 201-210 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsukita, S., at al.: "Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast : comparison with invasive ductal carcinoma"Histopathology. 42(1). 26-36 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsukita, S., et al.: "Expression of mucins (MUC1, MUC2, MUC5AC and MUC6) in mucinous carcinoma of the breast : comparison with invasive ductal carcinoma"Histopathology. 42・1. 26-36 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamada, S., et al.: "Expression of MUC1 and MUC2 mucins in extrahepatic bile duct carcinomas : Its relationship with tumor progression and prognosis"Pathol. Int.. 52・11. 713-723 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taki, C., et al.: "MUC1 mucin expression in follicular dendritic cells and lymphoepithelial lesion of gastric mucosa-associated lymphoid tissue lymphoma"Pathol. Int.. 52・11. 691-701 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 村田長芳, 他: "複合糖質の局在と機能"細胞. 34・14. 596-599 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Seko, A., et al.: "Ectopic expression of a GlcNAc 6-0-sulfotransferase, GlcNAc6ST-2, in colonic mucinous adenocarcinoma"Glycobiology. 12・6. 379-388 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yonezawa, S., et al.: "The expression of several types of mucin is related to the biological behavior of pancreatic neoplasms"J. Hepatobiliary Pancreat. Surg.. 9・3. 328-341 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ribeiro-Filho, L.A., et al.: "CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer"Mol. Carcinogen.. 34・4. 187-198 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 米澤傑, 他: "ムチンの発現様式からみた通常型膵管癌の組織発生-膵管内乳頭腫瘍との対比-"胆と膵. 23・3. 187-194 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshii, N., et al.: "Expression of mucin core proteins in extramammary Paget's disease"Pathol. Int.. 52・5/6. 390-399 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hasui, K., et al.: "Immunohistochemical analysis of the pathogenicity of Helicobacter pylori infection : Excess nitric oxide induced indirectly by Lewis X and Y is the cause of the pathogenicity of Helicobacter pylori infestation in the stomach"Acta Histochem. Cytochem.. 35・2. 93-100 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura, A., et al.: "New classification of pancreatic intraductal papillary-mucinous tumour by mucin expression : Its relationship with potential for malignancy"J. Pathol.. 197・2. 201-210 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuji, M., et al.: "Photoreceptor cell differentiation in retinoblastoma demonstrated by a new immunohistochemical marker mucin-like glycoprotein associated with photoreceptor cells (MLGAPC)"Histopathology. 40・2. 180-186 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura, A., et al.: "New classification of intraductal papillary-mucinous tumour by mucin expression : Its relationship with malignancy potential"The Journal of Pathology. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yonezawa, S., et al.: "Expression of several types of mucin are related to biological behavior of pancreatic neoplasms"Journal of Hepato-Biliary-Pancratic Surgery. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] 米澤 傑: "ムチンの発現様式からみた通常型膵管癌の組織発生-膵管内乳頭腫瘍との対比-"胆と膵. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Li, A., et al.: "Expression of MUC1 and MUC2 mucins and relationship with cell proliferative activity in human colorectal neoplasia"Pathology International. 51・11. 853-860 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wang, F., et al.: "Altered GalNAc-α-2, 6-sialylation compartments for mucin-associated sialyl-Tn antigen in colorectal adenoma and adenocarcinoma"The Journal of Histochemistry and Cytochemistry. 49・12. 1581-1592 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Li, A., et al.: "Comparative study for histology, proliferative activity, glycoproteins, and p53 protein between old and recent colorectal adenomas in Japan"Cancer Letters. 170・1. 45-52 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yonezawa,S., et al.: "Expression of mucin antigens and its relationship with malignancy"Handout of XXIII International Congress of the International Academy of Pathology. Short Course#03. 15-25 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Li,A.,Yonezawa,S., et al.: "Comparative study for histology, proliferative activity, glycoproteins, and p53 protein between old and recent colorectal adenomas in Japan"Cancer Letters. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Li,A., et al.: "Immunohistochemical estimation of in-situ cell cycle time in neoplastic epithelial cells in human large intestine : A new cell proliferation index"Human Cell. 13. 117-125 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wu,X., et al.: "Expression of mucin 1 (MUC1) in benign, premalignant and malignant vulvar tumors"Acta Histochemica et Cytochemica. 33. 267-273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukukura,T., et al.: "Intraductal papillary mucinous tumors of the pancreas : Thin-section helical CT findings"American Journal of Radiology. 174. 441-447 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Seko,A., et al.: "Biochemical differences between two types of N-acetylglucosamine : →6sulfotransferases in human colonic adenocarcinomas and adjacent normal mucos"Glycobiology. 10. 919-929 (2000)

    • Related Report
      2000 Annual Research Report

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

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