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Chen LX, Zou SJ, Li D, Zhou JY, Cheng ZT, Zhao J, Zhu YL, Kuang D, Zhu XH. Prostate-specific membrane antigen expression in hepatocellular carcinoma, cholangiocarcinoma, and liver cirrhosis. World J Gastroenterol 2020; 26:7664-7678. [PMID: 33505143 PMCID: PMC7789058 DOI: 10.3748/wjg.v26.i48.7664] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 10/09/2020] [Accepted: 11/29/2020] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Li-Xing Chen
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Si-Juan Zou
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Dan Li
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Jian-Yuan Zhou
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhao-Ting Cheng
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Jun Zhao
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
- School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Yuan-Li Zhu
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Dong Kuang
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xiao-Hua Zhu
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Abstract
Tumors of the liver, intrahepatic and extrahepatic bile ducts as well as the gallbladder are very heterogeneous and show different biological behavior. The 4‑stage (i.e. well, moderately, poorly and undifferentiated) grading system for hepatocellular carcinoma proposed by the WHO takes tumor size and architecture as well as the extent of cell and nuclear pleomorphism into account. In addition, the WHO defines some special forms of hepatocellular carcinoma. For carcinomas of intrahepatic bile ducts the WHO provides a 3‑stage (well, moderately and poorly differentiated) grading system, which is based on architectural and cytological changes. At this localization there are also additional special histological forms that have to be dealt with outside the grading system described. The WHO proposes a 3‑stage (well, moderately and poorly differentiated) grading system for carcinomas of the extrahepatic bile ducts and the gallbladder, which considers the proportion of glands contained within the adenocarcinoma. Similar to cancers of the liver and intrahepatic bile ducts there are also numerous special histological forms, which are explained in this article.
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Affiliation(s)
- H Jütte
- Institut für Pathologie, Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Deutschland.
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Deutschland.
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