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Molecular pathological analysis of oral carcinoma caused by chewing habits in Asia

Research Project

Project/Area Number 15256005
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Morphological basic dentistry
Research InstitutionNiigata University

Principal Investigator

SAKU Takashi  Niigata University, Institute of Medicine and dentistry, Professor (40145264)

Co-Investigator(Kenkyū-buntansha) CHENG Jun  Niigata University, Institute of Medicine and dentistry, Associate Professor (40207460)
MARUYAMA Satoshi  Niigata University, Institute of Medicine and dentistry, Assistant (30397161)
IDA Hiroko  Niigata University, Graduate School of Medical and dental Sciences, research fellow (60293213)
MIYAZAKI Hideo  Niigata University, Professor (00157629)
NAGAO Toru  Aichi Gakuin University, School of Dentistry, Lecturer (90261007)
浅川 義範  徳島文理大学, 薬学部, 教授 (50033874)
鈴木 誠  新潟大学, 医歯学総合病院, 講師 (50107778)
大城 和文  新潟大学, 大学院・医歯学総合研究科, 助手 (50332648)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥34,060,000 (Direct Cost: ¥26,200,000、Indirect Cost: ¥7,860,000)
Fiscal Year 2006: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2005: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2004: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2003: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
KeywordsAsia / oral cancer / carcinoma in-situ / epithelial dysplasia / submucosal fibrosis / extracellu matrix / chewing tobacco / pathological epidemiology / 口腔がん / 噛みたばこ / 表在型扁平上皮癌 / 前癌病変 / OSF / 歯科補綴物
Research Abstract

Oral cancers and its precancerous lesions were collected from Taiwan, India, Sri-Lanka, Bangladesh, Yemen, Madagascar, and Myanmar. Through the present collection of oral cancers and precancerous lesions, we have found lesions referred to as superficial carcinoma with or without the custom of chewing tobacco. The frequencies of oral carcinoma were shown to be related to chewing habits. The clinicopathological summary of superficial carcinoma in Japan was characterized by elder female patients, more commonly occurring in the tongue and gingival, less consumptions of tobacco for smoking and alcohol, but association with prosthetic treatments. In contrast, the lesion from Asian countries was found exclusively in the buccal mucosa and gingival, and the patients were mainly males with chewing habits. Histopathology of the superficial carcinoma of the Japanese and Asian patients resembled each other. They were commonly composed of carcinoma in-situ, which could be divided into three types, s … More uch as basaloid, verrucous, and acanthotic, and of surrounding epithelial dysplasia with the characteristic two-phase appearances. In addition, intraepithelial deposition of perlecan was demonstrated in epithelial dysplasia and carcinoma in-situ. This finding has been developed into a new concept of intraepithelial stroma. These two findings had greatly contributed to an objective histopathlogical diagnosis for oral borderline malignancies.
Using paraffin-embedded specimens collected from Asian countries, oral submucous fibrosis and superficial carcinomas were investigated in by immunohistochemistry and in-situ hybridization, PCR, and DNA sequencing techniques. Histopathologically, oral submucous fibrosis was graded with immunohistochemical patterns of extracellular matrix remodeling. The final status of oral submucous fibrosis was also shown to be poorly vascularized or hypoxic, which were important background for oral carcinogenesis. DNA samples obtained by microdissection were analyzed for mutational events in cancer-related genes. Among them, there were several characteristic mutations in the p53 gene which were shared by the collected cases, although samples from Asian countries were not always appropriate for DNA extraction and following experiments.
Samples of chewing staffs, such as betel, areca nuts, or qat, were organic-chemically demonstrated to have basically the same ingredients from area to area.
The data obtained in this study showed that oral carcinomas caused by different environmental factors shared similar genetic alterations and histopathological characteristics. Less

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (36 results)

All 2007 2006 2005 2004 Other

All Journal Article (31 results) Publications (5 results)

  • [Journal Article] High relative frequency of oral sgaumous cell carcinoma in Yemen:Qat and tobacco chewing as its aetiological background2007

    • Author(s)
      Sawair FA
    • Journal Title

      International Journal of environmental Health Research 17(3)

      Pages: 185-195

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] High relative frequency of oral sqaumous cell carcinoma in Yemen : Qat and tobacco chewing as its aetiological background2007

    • Author(s)
      Sawair FA, AL-Mutwakei A, AL-Eryani K, AL-Surhy A, Maruyama S, Cheng J, AL-Shaarbi A, Saku T
    • Journal Title

      International Journal of environmental Health Research 17(3)

      Pages: 185-195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] High relative frequency of oral squamous cell carcinoma in Yemen : Qat and tobacco chewing as its aetiological background2007

    • Author(s)
      Sawair FA
    • Journal Title

      Int J Envir Health Res 17(3)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pathogenesis of sudden round-shaped keratinization in carcinoma in-situ2007

    • Author(s)
      AI-Eryani K
    • Journal Title

      Proc Jpn Soc Pathol 96(1)

      Pages: 293-293

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 口腔2006

    • Author(s)
      朔 敬
    • Journal Title

      病理と臨床 24(S)

      Pages: 14-23

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Perlecan,a heparan sulfate proteoglycan,is a major constituent of the intraepithelial stroma functioning in tooth morphogenesis2006

    • Author(s)
      Ida-Yonemochi H
    • Journal Title

      Journal of Oral Biosciences 48(4)

      Pages: 233-243

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oral submucous fibrosis:Review on aetiology and pathogenesis2006

    • Author(s)
      Tilakaratne W M
    • Journal Title

      Oral Oncology 42(6)

      Pages: 561-568

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oral Mucosa2006

    • Author(s)
      Saku T
    • Journal Title

      Pathology and Clinical Medicine 24(S)

      Pages: 14-23

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Perlecan, a heparan sulfate proteoglycan, is a major constituent of the intraepithelial stroma functioning in tooth morphogenesis2006

    • Author(s)
      Ida-Yonemochi H, Saku T
    • Journal Title

      Journal of Oral Biosciences 48(4)

      Pages: 233-243

    • NAID

      10027102118

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oral submucous fibrosis : Review on aetiology and pathogenesis2006

    • Author(s)
      Tilakaratne W M, Klinikowski MF, Saku T, Peter TJ, Warnakulasuriya S
    • Journal Title

      Oral Oncology 42(6)

      Pages: 561-568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oral submucous fibrosis : review no aetiology and pathogenesis2006

    • Author(s)
      Tilakaratne WM
    • Journal Title

      Oral Oncol 42(6)

      Pages: 561-568

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differential expression modes of matrix metalloproteinases (MMPs) in oral borderline malignancies : an aid for histopathological recognition of dysplastic cell zone2006

    • Author(s)
      Tilakaratne WM
    • Journal Title

      Oral Med Pathol 11(1)

      Pages: 41-41

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 舌粘膜悪性境界病変における線維化の意義2006

    • Author(s)
      船山昭典
    • Journal Title

      日本口腔病理学会会誌 95(1)

      Pages: 286-286

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 口腔粘膜上皮悪性境界病変におけるいわゆる幹細胞マーカ分子の発現様式2006

    • Author(s)
      小林孝憲
    • Journal Title

      日本口腔病理学会会誌 95(1)

      Pages: 288-288

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Extracellular matrix remodeling in oral submucous fibrosis:its stage-specific modes revealed by immunohistochemistry and in situ hybridization2005

    • Author(s)
      Ustnomiya H
    • Journal Title

      Journal of Oral Pathology and Medicine 34(8)

      Pages: 498-507

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells2005

    • Author(s)
      Syafriadi M
    • Journal Title

      Journal of Oral Pathology and Medicine 34(6)

      Pages: 140-149

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Extracellular matrix remodeling in oral submucous fibrosis : its stage-specific modes revealed by immunohistochemistry and in situ hybridization2005

    • Author(s)
      Utsunomiya H, Tilakaratne WM, Oshiro K, Maruyama S, Suzuki M, Ida-Yonemochi H, Cheng J, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 34(8)

      Pages: 498-507

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Extracellular matrix remodeling in oral submucous fibrosis : its stage-specific modes revealed by immunohistochemistry and in situ hybridization2005

    • Author(s)
      Utsunomiya H
    • Journal Title

      J Oral Pathol Med 34(8)

      Pages: 498-507

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Perlecan, a basement membrane-type heparan sulfate proteoglycan, in the enamel organ : its intraepithelial localization in the stellate reticulum2005

    • Author(s)
      Ida-Yonemochi H
    • Journal Title

      J Histochem Cytochem 53(6)

      Pages: 763-772

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 口腔粘膜扁平上皮癌境界病変におけるリンパ管の分布様式.2005

    • Author(s)
      船山昭典
    • Journal Title

      J Oral Blosci 47(S)

      Pages: 122-122

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 「口腔粘膜表在性癌」の疾患概念の提唱:上皮内癌の病理組織学診断基準再検討を中心に2005

    • Author(s)
      朔 敬
    • Journal Title

      日本病理学会会誌 94(2)

      Pages: 20-20

    • Related Report
      2005 Annual Research Report
  • [Journal Article] New histopathological criteria for borderline malignancies of the oral mucosa2005

    • Author(s)
      Saku T
    • Journal Title

      Korean Journal of Oral and Maxillofacial Pathology 29(2)

      Pages: 151-152

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 口腔粘膜扁平上皮癌の浸潤とは腫瘍間質が誘導されることと同義である2005

    • Author(s)
      小林 孝憲
    • Journal Title

      日本病理学会会誌 94(1)

      Pages: 249-249

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Extracellular matrix remodeling in oral submucous fibrosis : its stage-specific modes revealed by immunohistochemistry and in-situ hybridization2005

    • Author(s)
      Utsunomiya H
    • Journal Title

      J Oral Pathol Med (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells2005

    • Author(s)
      Syafriadi M
    • Journal Title

      J Oral Pathol Med 34(3)

      Pages: 140-149

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 基底膜型ヘバラン硫酸プロテオグリカン・バールカンの上皮内配置:上皮内間質という新しい概念2004

    • Author(s)
      依田 浩子
    • Journal Title

      新潟歯学会雑誌 34(2)

      Pages: 247-249

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Intraepithelial expression of perlecan,a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epithelium2004

    • Author(s)
      Ikarashi T
    • Journal Title

      Journal of Oral Pathology and Medicine 33(2)

      Pages: 87-95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Perlecan, a basement membrane type heparan sulfate proteoglycan, in the epithelial space : a possibility of a new concept of intraepithelial stroma2004

    • Author(s)
      Ida-Yonemochi H, Saku T
    • Journal Title

      Niigata Dental Journal 34(2)

      Pages: 247-249

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epithelium2004

    • Author(s)
      Ikarashi T, Ida-Yonemochi H, Ohshiro K, Cheng J, Saku T
    • Journal Title

      Journal of Oral Pathology & Medicine 33(2)

      Pages: 87-95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Histopathological criteria for carcinoma in-situ of the oral mucosa confirmed by p53 gene mutation2004

    • Author(s)
      Syafriadi M
    • Journal Title

      日本病理学会会誌 93(1)

      Pages: 339-339

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 基底膜型ヘパラン硫酸プロテオグリカン・パールカンの上皮内配置:上皮内間質という新しい概念2004

    • Author(s)
      依田浩子
    • Journal Title

      新潟歯学会雑誌 34(2)

      Pages: 247-249

    • Related Report
      2004 Annual Research Report
  • [Publications] Yamazaki M: "Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues : a possible pathogenesis of cholesterol granulomas in jaw cysts"J Oral Pathol Med. 33(4). 177-184 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikarashi T: "Intraepithelial expression of perlecan, a basement membrane-type heparan sulfate proteoglycan reflects dysplastic changes of the oral mucosal epitnelium"J Oral Pathol Med. 33(2). 87-95 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Metwaly H: "Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion)"Virchows Arch. 443(1). 17-27 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jen KY: "Mutational events in LMP1 gene of Epstein-Barr virus in salivary gland lymphoepithelial carcinomas"Int J Cancer. 105(5). 654-660 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito M: "Jaw bone remodeling at the invasion front of gingival squamous cell carcinomas"J Oral Pathol Med. 32(1). 10-7 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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