A pathological study to establish new criteria for venous invasion in colorectal cancer

• Project/Area Number: 18K06999
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Toho University
• Principal Investigator: FUKASAWA Yuri 東邦大学, 医学部, 講師 (90392331)
• Co-Investigator(Kenkyū-buntansha): 藤澤 千恵 東邦大学, 医学部, 講師 (10393000) ; 三上 哲夫 東邦大学, 医学部, 教授 (90286352)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 血行性転移 / 大腸癌 / 腫瘍浸潤 / 静脈侵襲

Outline of Final Research Achievements

Using fifty colorectal cancer cases, histumbilicalal observations (HE and EvG staining) and immunohistochemistry for MMP7 and S100A4 were conducted. As a result, more than 5 lymph node metastases, non-contiguous venous invasion, and S100A4 expression of tumor cells were predictors of liver metastasis (sensitivity 85%, specificity 83%).
The addition of VEGFA or IL-8 to HUVEC (human umbilical vein endothelial cell) resulted in increased expression of pVE-cadherin.The results of the changes in colon cancer cell lines after the addition of butyric acid and TNF-alpha showed that DLD-1 reduced cell-cell adhesion, decreased CD44 expression, and increased migration ability, and WiDr decreased CD44 and increased CD44 extracellular cleavage (ELISA method). These results suggest that alteration of CD44 may be implicated in intravascular invasion in colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

進行大腸癌において、原発巣の病理組織学的所見のみでは予後予測は困難である。脈管侵襲を弾性線維染色を加えて判定することは重要だが、病理医間の判定一致率は低く、新たな所見およびマーカー分子の発見が必要と考えた。腫瘍細胞の脈管内侵入に焦点を当て、内皮細胞の変化および腫瘍細胞の結合性変化を起こす分子機構の一端を確認でき、新たなマーカー分子発見につながる所見を得ることができた。