Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2020; 26(48): 7664-7678
Published online Dec 28, 2020. doi: 10.3748/wjg.v26.i48.7664
Prostate-specific membrane antigen expression in hepatocellular carcinoma, cholangiocarcinoma, and liver cirrhosis
Li-Xing Chen, Si-Juan Zou, Dan Li, Jian-Yuan Zhou, Zhao-Ting Cheng, Jun Zhao, Yuan-Li Zhu, Dong Kuang, Xiao-Hua Zhu
Li-Xing Chen, Si-Juan Zou, Dan Li, Jian-Yuan Zhou, Zhao-Ting Cheng, Jun Zhao, Xiao-Hua Zhu, Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Jun Zhao, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Yuan-Li Zhu, Dong Kuang, Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Chen LX and Zhu XH conceived and designed the study; Zou SJ, Li D, Zhou JY, and Cheng ZT collected the clinical data; Zhu YL and Kuang D contributed to the analysis; Chen LX drafted the manuscript; Zhu XH, Zou SJ, Li D, Kuang D, and Zhu YL made the comments; Zhu XH critically reviewed and revised the manuscript; Zhao J polished the manuscript; All authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81873903, No. 81671718, No. 91959119 and No. 81271600; Natural Science Foundation of Hubei Province in China, No. 2016CFB687.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, No. 2019-S951.
Conflict-of-interest statement: We have no financial relationships to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xiao-Hua Zhu, MD, PhD, Professor, Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Ave, Wuhan 430030, Hubei Province, China. evazhu@vip.sina.com
Received: July 22, 2020
Peer-review started: July 22, 2020
First decision: September 30, 2020
Revised: October 9, 2020
Accepted: November 29, 2020
Article in press: November 29, 2020
Published online: December 28, 2020
Abstract
BACKGROUND

Primary liver cancer includes three subtypes: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and combined hepatocellular carcinoma. Patients with primary liver cancer experienced poor prognosis and high mortality, so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer. Prostate-specific membrane antigen (PSMA) expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently, but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited.

AIM

To study the expression of PSMA in HCC, CCA, and liver cirrhosis.

METHODS

A total of 446 formalin-fixed paraffin-embedded (FFPE) liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital. Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens (213 HCC, 203 CCA, and 30 liver cirrhosis). The tumor compartment and the associated neovascular endothelium were separately analyzed. PSMA expression was examined by two certified pathologists, and the final results were presented in a 4-point scoring system (0-3 points). Correlation between PSMA expression and clinicopathological information was also assessed.

RESULTS

PSMA was expressed primarily in the neovascular endothelium associated with tumors. The positive rate of PSMA staining in HCC was significantly higher than that in CCA (86.8% vs 79.3%; P = 0.001) but was only 6.6% in liver cirrhosis (P = 0.000). HCC cases had more 3-score PSMA staining than CCA had (89/213, 41.8% vs 35/203, 17.2%; P = 0.001). PSMA expression correlated positively with the stage and grade of HCC and CCA. In both liver cancer subtypes, there were more PSMA+ cases in stages III–V diseases than in stages I and II. High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage. There was no significant association of PSMA expression with sex, age, region, α-fetoprotein, hepatitis B surface antigen, or tumor size in both tumor subtypes.

CONCLUSION

Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.

Keywords: Prostate-specific membrane antigen, Hepatocellular carcinoma, Cholangiocarcinoma, Liver cirrhosis, Neovasculature, Immunohistochemistry

Core Tip: Immunohistochemistry was used to detect prostate-specific membrane antigen (PSMA) expression in hepatocellular carcinoma (HCC), cholangiocellular carcinoma (CCA), and liver cirrhosis. PSMA is specifically expressed in tumor-associated vasculature in HCC and CCA. The positive rate of PSMA staining in HCC was significantly higher than that in CCA (86.8% vs 79.3%), meanwhile, it was only 6.6% in liver cirrhosis, thus the potential of using PSMA-targeted imaging to distinguish HCC from liver cirrhosis may be true. PSMA expression correlated positively with stage and grade both in HCC and CCA; high staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage.