Epigenetic modification of micro RNA expression in serrated polyp-carcinoma pathway

• Project/Area Number: 21590394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• Principal Investigator: MITOMI Hiroyuki 独立行政法人国立病院機構(相模原病院臨床研究センター), 政策医療企画部, 研究員 (90181940)
• Co-Investigator(Kenkyū-buntansha): FUKUI Naoshi 独立行政法人国立病院機構相模原病院, 臨床研究センター・政策医療企画部, 研究員 (10251258) ; KANAZAWA Hideki 独立行政法人国立病院機構相模原病院, 臨床研究センター・統括診療部, 医長 (90265661)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: マイクロRNA / 鋸歯状ポリープ / 大腸腫瘍 / 遺伝子メチル化 / DNAミスマッチ修復遺伝子 / 消火器・唾液腺 / 大腸癌 / micro RNA / Pathched / EphB2 / 消化器・唾液腺 / 大腸 / ポリープ / microRNA

Research Abstract

Serrated polyp including sessile and traditional serrated polyp/adenoma is a precursor to a subset of microsatellite-unstable colorectal carcinoma. In contrast, hyperplastic polyp is considered to have very low risk of progression to carcinoma. Histological discrimination is sometimes difficult and problematic between two polyps because of both having architectural similarities. We found a differential expression of microRNA 20, 21, 93 and 181b in serrated and hyperplastic polyps. We have further shown that loss of mismatch repair protein hMLH1 expression, probably as a result of gene methylation, is inversely correlated with microRNA 21 and 93 in serrated polyp. Our results point toward a potential target therapy of these microRNA in serrated polyp development or progression.

Research Products

• [Journal Article] Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas (2012)
  • Author(s): Imamhasan A, Mitomi H, Saito T, Hayashi T, Takahashi M, Kajiyama Y, Yao T.
  • Journal Title: Hum Pathol
• [Journal Article] Clear cell variant of squamous cell carcinoma originating in the esophagus : report of a case with immunohistochemical and oncogenetic analyses (2012)
  • Author(s): Imamhasan A, Mitomi H, Saito T, Arakawa A, Yao T.
  • Journal Title: Pathol Int Volume: 62(2) Pages: 137-43
  • NAID: 10031185179
• [Journal Article] Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients (2012)
  • Author(s): Nakai K, Mitomi H, Alkam Y, Arakawa A, Yao T, Tokuda E, Saito M, Kasumi F.
  • Journal Title: Cancer Chemother Pharmacol Volume: 69(4) Pages: 923-30
• [Journal Article] Clear cell variant of squamous cell carcinoma originating in the esophagus : Report of a case with immunohistochemical and oncogenetic analyses (2012)
  • Author(s): Imamhasan A, Mitomi H (Equal contribution to the first author), Saito T, Arakawa A, Yao T
  • Journal Title: Pathol Int Volume: 62 Issue: 2 Pages: 137-143
  • DOI: 10.1111/j.1440-1827.2011.02758.x
  • NAID: 10031185179
  • Peer Reviewed
• [Journal Article] Role for p16(INK4a) in progression of gastrointestinal stromal tumors of the stomach : alteration of p16(INK4a) network members (2011)
  • Author(s): Mitomi H, Fukui N, Kishimoto I, Tanabe S, Kikuchi S, Saito T, Hayashi T, Yao T.
  • Journal Title: Hum Pathol Volume: 42(10) Pages: 1505-13
• [Journal Article] Cluster analysis of claudin-1 and-4, E-cadherin, andβ-catenin expression in colorectal cancers (2011)
  • Author(s): Matsuoka T, Mitomi H, Fukui N, Kanazawa H, Saito T, Hayashi T, Yao T.
  • Journal Title: J Surg Oncol Volume: 103(7) Pages: 674-86
• [Journal Article] αvβ5 integrin promotes dedifferentiation of monolayer-cultured articular chondrocytes (2011)
  • Author(s): Fukui N, Ikeda Y, Tanaka N, Wake M, Yamaguchi T, Mitomi H, Ishida S, Furukawa H, Hamada Y, Miyamoto Y, Sawabe M, Tashiro T, Katsuragawa Y, Tohma S
  • Journal Title: Arthritis Rheum Volume: 63(7) Pages: 1938-49
• [Journal Article] 癌併存大腸広基性鋸歯状腺腫/ポリープの臨床病理学的特徴 (2011)
  • Author(s): 三富弘之,五十嵐誠治,伴慎一,九嶋亮治,藤田恒平,平橋美奈子,大城由美,林大久生,八尾隆史
  • Journal Title: 胃と腸 Volume: 46 Pages: 384-93
• [Journal Article] 大腸癌-最近の研究動向-III大腸癌の分子生物学と発癌機序発癌機序大腸鋸歯状病変の癌化 (2011)
  • Author(s): 三富弘之,林大久生, Alkam Yimit,八尾隆史
  • Journal Title: 日本臨床 Volume: 69 Pages: 115-120
• [Journal Article] 大腸SSA/Pの病理組織学的特徴と診断基準大腸癌研究会プロジェクト研究から (2011)
  • Author(s): 八尾隆史,菅井有,岩下明徳,藤盛孝博,九嶋亮治,野首光弘,三富弘之,味岡洋一,小西文雄
  • Journal Title: 胃と腸 Volume: 46 Pages: 442-8
• [Journal Article] Cluster analysis of claudin-1 and -4, E-cadherin, and β-catenin expression in colorectal cancers (2011)
  • Author(s): Matsuoka T, Mitomi H (Equal contribution to the first author), Fukui N, Kanazawa H, Saito T, Hayashi T, Yao T
  • Journal Title: J.Surg.Oncol. Volume: 103 Issue: 7 Pages: 674-686
  • DOI: 10.1002/jso.21854
  • Peer Reviewed
• [Journal Article] Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients (2011)
  • Author(s): Nakai K, Mitomi H (Equal contribution to the first author), Alkam Y, Arakawa A, Yao T, Tokuda E, Saito M, Kasumi F
  • Journal Title: Cancer Chemoth Pharm Volume: 69 Pages: 923-930
  • Peer Reviewed
• [Journal Article] Aberrant p16((INK4a)) methylation is a frequent event in colorectal cancers : prognostic value and relation to mRNA expression and immunoreactivity (2010)
  • Author(s): Mitomi H, Fukui N, Tanaka N, Kanazawa H, Saito T, Matsuoka T, Yao T.
  • Journal Title: J Cancer Res Clin Oncol Volume: 136(2) Pages: 323-31
• [Journal Article] Changes of human menisci in osteoarthritic knee joints (2010)
  • Author(s): Katsuragawa Y, Saitoh K, Tanaka N, Wake M, Ikeda Y, Furukawa H, Tohma S, Sawabe M, Ishiyama M, Yagishita S, Suzuki R, Mitomi H, Fukui N.
  • Journal Title: Osteoarthritis Cartilage Volume: 18(9) Pages: 1133-43
• [Journal Article] Aberrant p16^<INK4a> methylation is a frequent event in colorectal cancers : prognostic value and relation to mRNA expression and immunoreactivity (2010)
  • Author(s): 三富弘之, 福井尚志, 田中信帆, 金澤秀紀, 齋藤剛, 松岡隆, 八尾隆史
  • Journal Title: J.Cancer.Res.Clin.Oncol. 136 Pages: 323-331
  • Peer Reviewed
• [Presentation] Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas (2012)
  • Author(s): Imamhasan Abdukadir、三富弘之、齋藤剛、林大久夫、荒川敦、内田士郎、福村由紀、三谷恵子、八尾隆史
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] 食道上皮内腫瘍におけるポリコーム蛋白EZH2, Bmi-1発現の検討 (2012)
  • Author(s): 内田士郎、三富弘之、齋藤剛、Abdukadir Imamhasan、増田芳雄、和田了、八尾隆史
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-26
• [Presentation] Basal-like乳癌(BL C)におけるEGER, cytokeratin(CK) 5/6/14/17, c-kit発現とclinical outcome (2011)
  • Author(s): アリカムイミティ、三富弘之、中井克也、齊藤光江、霞富士雄
  • Organizer: 第19回日本乳癌学会総会
  • Place of Presentation: 仙台
• [Presentation] 胃間質細胞腫瘍(GIST)におけるp16INK4a(p16)/Retinoblastoma(Rb)経路の破綻とその臨床病理学的意義 (2010)
  • Author(s): 三富弘之、松岡隆、齋藤剛、林大久夫、八尾隆史
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] Claudin-1, Claudin-4, E-cadherin,β-cateninの発現低下は大腸癌における予後不良因子である (2010)
  • Author(s): 松岡隆、三富弘之、齋藤剛、林大久夫、八尾隆史
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] デスモイド腫瘍におけるβ-cateninの遺伝子異常のタイプと標的遺伝子の活性化能および細胞増殖能の比較検討 (2010)
  • Author(s): 齋藤剛、三富弘之、三谷恵子、八尾隆史
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京