Solid-type poorly differentiated adenocarcinoma of the stomach: A characteristic morphology reveals a distinctive immunoregulatory tumor microenvironment

Shinichiro Kawatoko, Kenichi Kohashi, Takehiro Torisu, Taisuke Sasaki, Shinya Umekita, Eiji Oki, Masafumi Nakamura, Takanari Kitazono, Yoshinao Oda

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Solid-type poorly differentiated adenocarcinoma (solid-type-PDA) of the stomach is a unique histological subtype of “tubular adenocarcinoma”, but little is known about its clinicopathological features, molecular pathological characteristics and immunoregulatory tumor microenvironment. Herein, we examined the immunohistochemical expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6) in 57 cases of solid-type-PDA and classified them as either MMR-deficient or -proficient (dMMR, N = 23; pMMR, N = 34), and additionally identified 18 dMMR-well-differentiated adenocarcinoma (WDA) and 34 pMMR-WDA as control groups. We analyzed and compared solid-type-PDA with WDA by evaluating the immunoexpressions of key immune pathway proteins (programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1)) and tumor-infiltrating lymphocytes (TILs) (CD8, Foxp3 and PD-1). The results reveled IDO1 was significantly more frequent in dMMR-solid-type-PDA than in dMMR-WDA (P = 0.0046). Moreover, dMMR-solid-type-PDA tended to have higher mean CD8+ and Foxp3+ TILs compared with dMMR-WDA [P = 0.0006 (CD8+) and P = 0.1061 (Foxp3+)], and IDO1-positive tended to be associated with a large number of CD8+, Foxp3+ or PD‐1+ TILs in almost all tumor subtypes. PD-L1 was significantly observed in 44 % (15/34) of pMMR-solid-type-PDA compared with 18 % (6/34) of pMMR-WDA (P = 0.0344). Although they are molecularly and morphologically classified as the same chromosomal instability subtype, overall survival (OS) and disease-free-survival (DFS) in pMMR-solid-type-PDA were significantly worse than those in pMMR-WDA [P = 0.0216 (OS) and P = 0.0160 (DFS)]. Our study demonstrates that immunoexpressions of several immunoregulatory proteins and TILs are more prevalent in dMMR-solid-type-PDA, potentially a useful discovery for designing tumor treatments with immune checkpoint inhibitors or combination therapies with a PD-1/PD-L1-inhibitor and IDO1-inhibitor.

本文言語英語
論文番号154124
ジャーナルPathology Research and Practice
238
DOI
出版ステータス出版済み - 10月 2022
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 病理学および法医学
  • 細胞生物学

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