Pathological Analysis of Carcinogenesis Mechanism of Triple Negative Breast Cancer from the Viewpoint of Cancer Microenvironment

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06934
• 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: Kawasaki Medical School
• Principal Investigator: Moriya Takuya 川崎医科大学, 医学部, 教授 (00230160)
• Co-Investigator(Kenkyū-buntansha): 紅林 淳一 川崎医療福祉大学, 医療技術学部, 教授 (10248255) ; 西村 広健 川崎医科大学, 医学部, 講師 (70368661)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 乳癌 / 病理 / 非浸潤性乳管癌 / 免疫組織化学 / 早期癌 / 非浸潤癌 / B7-H4 / P4HA

Outline of Final Research Achievements

Pathological analysis was performed with the aim of clarifying the influence of the environment surrounding breast cancer on the process of cancer development and progression.
In invasive breast cancer, P4H, especially P4HA2, which is related to collagen metabolism, correlated with cancer grade and was also associated with ischemia at the tumor site. P4H2 expression was similar in early-stage cancer, noninvasive ductal carcinoma in situ (DCIS) period. In triple negative breast cancer with treatment-resistant and poor prognosis, immune activity was low in the androgen receptor (AR) positive group and high in the negative group, and the latter was further divided into two groups with different B7-H4 and IDO1 expression status. expression of PD-L1 and ischemic markers was lower in DCIS compared to invasive carcinoma, presumably due to the lack of stromal invasion and poor interaction with the surrounding environment.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

コラーゲン代謝に関係する物質のP4H、特にP4HA2は悪性度の高い乳癌で高発現することから、乳癌における新たなバイオマーカーになる可能性がある。このことは、早期の癌である非浸潤性乳管癌の段階から確認することができることも示した。
トリプルネガティブ乳癌は、AR、IDO1、B7-H4の3つによって、腫瘍を取り巻く3つの群に分かれることを証明した。これら3者に対する新しい治療薬がそれぞれ開発中であり、患者の選択や治療効果の推定をする上で参考になりえる基礎データを提供した。