Analysis of the relationship between cellular differentiation and involving genomes in colorectal tumors

• Project/Area Number: 16590299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Fujita Health University
• Principal Investigator: INADA Ken-ichi Fujita Health University, School of Medicine, Assistant Professor, 医学部, 助教授 (70246081)
• Co-Investigator(Kenkyū-buntansha): TSUKAMOTO Tetsuya Aichi Cancer Center Research Institute, Division of Oncological Pathology, Section Head, 腫瘍病理学部, 室長 (00236861)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: Colorectal Tumor / Early Cancer / Cellular Differentiation / MUC2 / MUC5AC / Cdx2 / Adenoma-Carcinoma Sequence / de nove Cancer / HGM / MUC6 / βカテニン / p53

Research Abstract

We examined the correlation between the gastric and intestinal phenotypic expression and the colorectal carcinogenesis in the early carcinomas of colon. We evaluated 91 primary early colorectal carcinomas, including the adjacent adenomatous components, histologically and phenotypically. The MUC2 expression had the significant decrease from tubular/tublovillous adenomas with moderate atypia, through intramucosal carcinomas, to the cancers of submucosal invasion with progression (P<0.0001). The intramucosal de novo carcinomas (flat type carcinomas without adenomatous components) had more decrease of MUC2 expression than the intramucosal lesions with adenomatous components. MUC5AC expression decreased statistically according to the adenoma-carcinoma sequence, while the carcinomas with villous adenomatous components had the high level of MUC5AC expression compared with those of tubular adenomatous counterparts, suggesting a pathway of malignant transformation different from that of tubular tumors. Cdx2 nuclear expression was maintained in all adenomas and early carcinomas of colon. In conclusion, our data suggest that the reduction of MUC2 expression is important for the occurrence and progression of colorectal carcinomas in both adenoma-carcinoma sequence pathway and de novo carcinogenesis. The tumor-suppressive effects of Cdx2 may be kept at the early stage of colorectal carcinogenesis.

Research Products

• [Journal Article] Mixed gastric- and intestinal-type metaplasia is formed by cells with dual intestinal and gastric differentiation. (2005)
  • Author(s): Niwa T, Inada K, et al.
  • Journal Title: J. Histochem. Cytochem. 53 Pages: 75-85
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Paneth type gastric cancer cells exhibit expression of human defensin-5. (2005)
  • Author(s): Inada K, Mizoshita T, et al.
  • Journal Title: Histopathology 47 Pages: 330-331
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Coexistence of gastric and intestinal type endocrine cells in gastric-and-intestinal mixed intestinal metaplasia of the human stomach. (2005)
  • Author(s): Otsuka T, Inada K, et al.
  • Journal Title: Pathol. Int. 55 Pages: 170-179
  • NAID: 10016474960
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts. (2005)
  • Author(s): Hamamoto A, Inada K, et al.
  • Journal Title: Int. J. Oncol. 26 Pages: 891-896
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibitory effect of etodolac, a selective cyslooxygenasse-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils. (2005)
  • Author(s): Magari H, Inada K, et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 334 Pages: 606-612
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Loss of p21(WAF1/CIP1) expression in invasive fronts of oral tongue squamous cell carcinomas is correlated with tumor progression and poor prognosis. (2005)
  • Author(s): Goto M, Inada K, et al.
  • Journal Title: Oncol. Rep. 14 Pages: 837-846
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mixed gastric- and intestinal-type metaplasia is formed by cells with dual intestinal and gastric differentiation. (2005)
  • Author(s): Niwa, T., Ikehara, Y., Nakanishi, H., Tanaka, H., Inada, K., Tsukamoto, T., Ichinose, M., Tatematsu, M.
  • Journal Title: J.Histochem.Cytochem. 53 Pages: 75-85
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Paneth type gastric cancer cells exhibit expression of human defensin-5. (2005)
  • Author(s): Inada, K., Mizoshita, T., Tsukamoto, T., Porter, E.M., Tatematsu, M.
  • Journal Title: Histopathology 47 Pages: 330-331
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Coexistence of gastric and intestinal type endocrine cells in gastric-and-intestinal mixed intestinal metaplasia of the human stomach. (2005)
  • Author(s): Otsuka, T., Tsukamoto, T., Mizoshita, T., Inada, K., Takenaka, Y., Kato, S., Yamamura Y., Miki, K., Tatematsu, M.
  • Journal Title: Pathol.Int. 55 Pages: 170-179
  • NAID: 10016474960
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts. (2005)
  • Author(s): Hamamoto, A., Abe, Y., Nishi M., Fujimori, S., Ohnishi, Y., Yamazaki, H., Oida, Y., Miyazaki, N., Inada, K., Ueyama, Y., Iwasaki, M., Inoue, H., Nakamura, M.
  • Journal Title: Int.J.Oncol. 26 Pages: 891-896
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibitory effect of etodolac, a selective cyslooxygenasse-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils. (2005)
  • Author(s): Magari, H., Shimizu, Y, Inada, K., Enomoto, S., Tomeki, T., Yanaoka, K., Tamai, H., Arii, K., Nakata, H., Oka, M., Utsunomiya, H., Tsutsumi, Y., Tsukamoto, T., Tatematsu, M., Ichinose, M.
  • Journal Title: Biochem.Biophys.Res.Commun. 334 Pages: 606-612
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Loss of p21(WAF1/CIP1) expression in invasive fronts of oral tongue squamous cell carcinomas is correlated with tumor progression and poor prognosis. (2005)
  • Author(s): Goto, M., Tsukamoto, T., Inada, K., Mizoshita, T., Ogawa, T., Terada, A., Hyodo, I., Shimozato, K., Hasegawa, Y., Tatematsu, M.
  • Journal Title: Oncol.Rep. 14 Pages: 837-846
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mixed gastric- and intestinal-type metaplasia is formed by cells with dual intestinal and gastric differentiation. (2005)
  • Author(s): Niwa T, Inada K, et al.
  • Journal Title: J.Histochem.Cytochem. 53 Pages: 75-85
• [Journal Article] Coexistence of gastric and intestinal type endocrine cells in gastric-and-intestinal mixed intestinal metaplasia of the human stomach. (2005)
  • Author(s): Otsuka T, Inada K, et al.
  • Journal Title: Pathol.Int. 55 Pages: 170-179
  • NAID: 10016474960
• [Journal Article] Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts. (2005)
  • Author(s): Hamamoto A, Inada K, et al.
  • Journal Title: Int.J.Oncol. 26: Pages: 891-896
• [Journal Article] Inhibitory effect of etodolac, a selective cyslooxygenasse-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils. (2005)
  • Author(s): Magari H, Inada K, et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 334 Pages: 606-612
• [Journal Article] Loss of p21(WAF1/CIP1) expression in invasive fronts of oral tongue squamous cell carcinomas is correlated with tumor progression and poor prognosis. (2005)
  • Author(s): Goto M, Inada K, et al.
  • Journal Title: Oncol.Rep. 14 Pages: 837-846
• [Journal Article] Appropriate epitope retrieval for c-kit protein immunostaining in routinely prepared specimens of gastrointestinal stromal tumor. (2004)
  • Author(s): Matsuyama, A., Inada, K., et al.
  • Journal Title: Acta Histochem.Cytochem. 37 Pages: 87-93
  • NAID: 110003144369
• [Journal Article] Characterization of monoclonal antibody, HTA28, recognizing a his-tone H3 phozphorylation site as a useful marker of M-phase cells. (2004)
  • Author(s): Hirata, A., Inada, K., et al.
  • Journal Title: J.Histochem.Cytochem. 52 Pages: 1503-1509
• [Journal Article] Endoscopic ultrasound-guided fine-needled aspiration biopsy for the diagnosis of gastrointestinal stromal tumors in the stomach. (2004)
  • Author(s): Okubo, K., Inada, K., et al.
  • Journal Title: J.Gastroenterol. 39 Pages: 747-753
  • NAID: 80016835117
• [Journal Article] Treatment and risk factors for recurrence after curative resection of gastrointestinal stromal tumors of the stomach. (2004)
  • Author(s): Mochizuki, Y., Inada, K., et al.
  • Journal Title: World J.Surg. 28 Pages: 870-875
• [Journal Article] Use of 11p15 mucins as prognostic factors in small adenocarcinoma of the lung. (2003)
  • Author(s): Nishiumi, N., Inada, K., et al.
  • Journal Title: Clin.Cancer Res. 9 Pages: 5616-5619
• [Journal Article] Immunohistochemical demonstration of dihydropyrimidine dehydrogenase in normal and cancerous tissues. (2003)
  • Author(s): Kamoshida S., Inada, K., et al.
  • Journal Title: Acta Histochem.Cytochem. 36 Pages: 471-479
  • NAID: 110003144304