Clinical significance of mechanistic target of rapamycin expression in vessels that encapsulate tumor cluster-positive hepatocellular carcinoma patients who have undergone living donor liver transplantation

Katsuya Toshida; Shinji Itoh; Takeo Toshima; Shohei Yoshiya; Ryoichi Goto; Atsuyoshi Mita; Noboru Harada; Kenichi Kohashi; Yoshinao Oda; Tomoharu Yoshizumi

doi:10.1002/ags3.12735

Clinical significance of mechanistic target of rapamycin expression in vessels that encapsulate tumor cluster-positive hepatocellular carcinoma patients who have undergone living donor liver transplantation

Ann Gastroenterol Surg. 2023 Aug 28;8(1):163-171. doi: 10.1002/ags3.12735. eCollection 2024 Jan.

Authors

Affiliations

¹ Department of Surgery and Science, Graduate School of Medical Sciences Kyushu University Fukuoka Japan.
² Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan.
³ Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation, and Pediatric Surgery, Department of Surgery Shinshu University School of Medicine Nagano Japan.
⁴ Department of Anatomic Pathology, Graduate School of Medical Sciences Kyushu University Fukuoka Japan.

Abstract

Background: There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)-positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT).

Methods: Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin-2 (Ang-2) in VETC-positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions.

Results: Forty-three of the 214 patients (20.1%) were VETC-positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang-2 expression was significantly higher in the mTOR-positive than in the mTOR-negative group (p = 0.037). Thirty-four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC-positive; five of these six patients also had VETC-positive recurrent lesions (p < 0.001). The expression of mTOR was significantly higher in the VETC-positive lesions (p = 0.0018).

Conclusions: We showed that mTOR expression was higher in the VETC-positive primary and recurrent lesions than in the VETC-negative ones.

Keywords: everolimus; hepatocellular carcinoma; living donor liver transplantation; mechanistic target of rapamycin; vessels that encapsulate tumor cluster.