Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2019; 11(3): 294-304
Published online Mar 27, 2019. doi: 10.4254/wjh.v11.i3.294
Angiogenesis of hepatocellular carcinoma: An immunohistochemistry study
Decebal Fodor, Ioan Jung, Sabin Turdean, Catalin Satala, Simona Gurzu
Decebal Fodor, Ioan Jung, Sabin Turdean, Catalin Satala, Simona Gurzu, Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, Targu Mures 530149, Romania
Simona Gurzu, Research Center (CCAMF), University of Medicine, Pharmacy, Sciences and Technology, Targu Mures 540139, Romania
Author contributions: Fodor D drafted the article and contributed to the surgical interventions; Jung I contributed to the diagnosis and immunohistochemical assessment; Turdean S contributed to the conception of the paper, angiogenesis and statistical assessment; Satala C contributed to the statistical assessment; Gurzu S designed research and confer the final agreement for publication; Fodor D and Turdean S had equal contribution to the paper.
Institutional review board statement: The agreement of the Ethical Committee of University of Medicine and Pharmacy, Targu Mures, Romania, was obtained.
Conflict-of-interest statement: None declared.
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: Simona Gurzu, MD, PhD, Professor, Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, 38 Gheorghe Marinescu Street, Targu Mures 530149, Romania. simona.gurzu@umftgm.ro
Telephone: +40-745-673550 Fax: +40-265-210407
Received: December 28, 2018
Peer-review started: December 29, 2018
First decision: January 27, 2019
Revised: January 27, 2019
Accepted: March 12, 2019
Article in press: March 12, 2019
Published online: March 27, 2019

Although hepatocellular carcinoma (HCC) is one of the most vascular solid tumors, antiangiogenic therapy has not induced the expected results.


To uncover immunohistochemical (IHC) aspects of angiogenesis in HCC.


A retrospective cohort study was performed and 50 cases of HCC were randomly selected. The angiogenesis particularities were evaluated based on the IHC markers Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) A and the endothelial area (EA) was counted using the antibodies CD31 and CD105.


The angiogenic phenotype evaluated with VEGF-A was more expressed in small tumors without vascular invasion (pT1), whereas COX-2 was rather expressed in dedifferentiated tumors developed in non-cirrhotic liver. The CD31-related EA value decreased in parallel with increasing COX-2 intensity but was higher in HCC cases developed in patients with cirrhosis. The CD105-related EA was higher in tumors developed in patients without associated hepatitis.


In patients with HCC developed in cirrhosis, the newly formed vessels are rather immature and their genesis is mediated via VEGF. In patients with non-cirrhotic liver, COX-2 intensity and number of mature neoformed vessels increases in parallel with HCC dedifferentiation.

Keywords: Hepatocellular carcinoma, Angiogenesis, Endothelial area, Antiangiogenic therapy

Core tip: In this paper we showed a possible role of morphological and immunohistochemical features of Hepatocellular carcinoma (HCC) in predicting the individualized antiangiogenic therapy of HCC. Based on the results and literature data, it seems that dedifferentiated HCCs developed in non-cirrhotic liver are predominantly driven via Cyclooxygenase-2 axis, whereas vascular endothelial growth factor-A induces hepatocarcinogenesis in patients with HCCs developed on the cirrhosis background.