Analysis of significance of histological classification of adenocarcinoma with enteroblastic differentiation in the digestive tract, especially in association with its aggressiveness.

• Project/Area Number: 17K08704
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Juntendo University
• Principal Investigator: Yao Takashi 順天堂大学, 医学部, 教授 (20243933)
• Co-Investigator(Kenkyū-buntansha): 齋藤 剛 順天堂大学, 医学部, 准教授 (80439736)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃癌 / 大腸癌 / 胎児消化管類似癌 / TP53 / HER2 / SMAD4 / MSI / 高悪性度 / 肝様腺癌 / LOH / メチル化 / TET1 / 5-hmC / 胎児消化管上皮類似癌 / AFP / SALL4 / Glypican 3 / 消化管

Outline of Final Research Achievements

From 2273 cases of gastric adenocarcinoma, 51 cases (2.2%) of gastric adenocarcinoma with enteroblastic differentiation (AED) were selected for this study. By the clinicopathological analysis, it was confirmed that gastric AED was highly aggressive. Furthermore, it was also suggested that hepatoid adenocarcinoma should be included as a gastric AED showing solid growth. In gastric AED, TP53 gene mutation was found to be more frequent, and HER2 overexpression was more frequent than that in normal cancer. Furthermore, SMAD4 was considered to be one of the associated genes.
The presence of AED was also confirmed in colorectal cancer, and it was also revealed that it is a highly aggressive, but the histological classification including the relationship between histological features and fetal gut markers is an issue for the future. The results of these analysis may be useful for future treatment strategies for gastric and colorectal cancers.

Academic Significance and Societal Importance of the Research Achievements

胃の胎児消化管類似癌(AED)は高悪性度の癌であり、TP53遺伝子変異とHER2過剰発現が高頻度であり、SMAD4も関連性のある遺伝子のひとつであることが示された。大腸癌でもAEDの存在と高悪性度の癌であることが確認された。これらの解析結果は胃癌・大腸癌の今後の治療戦略に有用であると思われる。

Research Products

• [Journal Article] Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological study of five cases. (2020)
  • Author(s): Murakami T, Yao T, Yatagai N, Yamashiro Y, Saito T, Sakamoto N, Nagahara A.
  • Journal Title: Histopathology Volume: 76 Issue: 2 Pages: 325-332
  • DOI: 10.1111/his.13973
  • Peer Reviewed
• [Journal Article] Molecular and clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation. (2020)
  • Author(s): 3.Yamashiro Y, Saito T, Hayashi T, Murakami T, Yanai Y, Tsuyama S, Suehara Y, Takamochi K, Yao T.
  • Journal Title: Histopathol Volume: in press Issue: 3 Pages: 492-502
  • DOI: 10.1111/his.14158
  • Peer Reviewed
• [Journal Article] Hepatoid adenocarcinoma with enteroblastic differentiation in the sigmoid colon: lesions from a rare case. (2019)
  • Author(s): Ogiwara S, Furihata M, Fukami K, Yamashita A, Yao T, Osada T.
  • Journal Title: Am J Gastroenterol Volume: 114 Issue: 4 Pages: 684-685
  • DOI: 10.14309/ajg.0000000000000176
  • Peer Reviewed
• [Journal Article] Frequent loss of heterozygosity of SMAD4 locus and prognostic impacts of SMAD4 immunohistochemistry in gastric adenocarcinoma with enteroblastic differentiation. (2019)
  • Author(s): Yatagai N, Saito T, Akazawa Y, Hayashi T, Yanai Y, Tsuyama S, Murakami T, Ueyama H, Watanabe S, Nagahara A, Yao T.
  • Journal Title: Hum Pathol Volume: 88 Pages: 18-26
  • DOI: 10.1016/j.humpath.2019.03.005
  • Peer Reviewed
• [Journal Article] TP53 inactivation and expression of methylation-associated proteins in gastric adenocarcinoma with enteroblastic differentiation. (2019)
  • Author(s): 2.Yatagai N, Saito T, Akazawa Y, Hayashi T, Yanai Y, Tsuyama S, Ueyama H, Murakami T, Watanabe S, Nagahara A, Yao T.
  • Journal Title: Virchows Arch Volume: 474 Issue: 3 Pages: 315-324
  • DOI: 10.1007/s00428-018-2508-9
  • Peer Reviewed
• [Journal Article] Next-generation sequencing analysis for gastric adenocarcinoma with enteroblastic differentiation: emphasis on the relationship with hepatoid adenocarcinoma. (2018)
  • Author(s): 1.Akazawa Y, Saito T, Hayashi T, Yanai Y, Tsuyama S, Akaike K, Suehara Y, Takahashi F, Takamochi K, Ueyama H, Murakami T, Watanabe S, Nagahara A, Yao T.
  • Journal Title: Hum Pathol Volume: 78 Pages: 79-88
  • DOI: 10.1016/j.humpath.2018.04.022
  • Peer Reviewed / Open Access