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

Author:

Toshida Katsuya1,Itoh Shinji1ORCID,Toshima Takeo1ORCID,Yoshiya Shohei1ORCID,Goto Ryoichi2ORCID,Mita Atsuyoshi3ORCID,Harada Noboru1,Kohashi Kenichi4,Oda Yoshinao4,Yoshizumi Tomoharu1ORCID

Affiliation:

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

AbstractBackgroundThere 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).MethodsUsing 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.ResultsForty‐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).ConclusionsWe showed that mTOR expression was higher in the VETC‐positive primary and recurrent lesions than in the VETC‐negative ones.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Gastroenterology,Surgery

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