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
Research background

Although hepatocellular carcinoma (HCC) is one the most vascular solid tumors, mechanisms of angiogenesis are still unknown. Moreover, angiogenesis is not properly inhibited by the currently used chemotherapics. For these reasons, new data are necessary to be published regarding the angiogenesis background.

Research motivation

The aim of the study was to perform a complex immunohstochemical assessment of angiogenic immunophenotype pf HCC cells.

Research objectives

In this paper, we aimed to correlate the angiogenic immunophenotype of tumor cells with the values of endothelial area (EA). To reach the aim of the paper and understand the angiogenesis mechanisms, these two parameters were necessary to be examined.

Research methods

The angiogenic immunophenotype of tumor cells was examined with the immunohisto-chemically antibodies Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) A, whereas the values of EA were quantified using the antibodies CD31 and CD105. To increase the study reliability, the EA was digitally counted, using a semi automatically method.

Research results

The immunohistochemical study performed in this paper showed that the VEGF-A-related angiogenesis is more intense in small tumors, without vascular invasion, which were classified as pT1 HCCs. In the dedifferentiated and aggressive tumors, COX-2 was more expressed and CD31-related EA decreased, as result of proliferation of mature neoformed vessels. In patients with associated cirrhosis, CD31-related EA was higher, as result of proliferation of immature vessels. In patients without associated hepatitis, CD105-related EA was higher, as result of activated endothelial cells.

Research conclusions

The original data identified in the present study showed that the antiangiogenic therapy do not show the expected results for several reasons: angiogenesis has an oscillating pattern, the mechanisms of inducing angiogenesis depend on the tumor size and grade of differentiation and the EA is not always a reflection of the angiogenesis intensity. Based on these data, it can be concluded that a targeted antiangiogenic therapy should be considered in patients with HCC, based on the pathways of induction angiogenesis in specific cases.

Research perspectives

Before performing clinical trials with antiangiogenic/antityrosine-kinase drugs, the immunohistochemical and molecular background of the tumor tissue is mandatory to be checked in any patient. It should be tested, in experimental study, the theory of predominance of VEGF-A-induced angiogenesis in small differentiated HCCs and COX-2 induced angiogenesis and vascular maturation in dedifferentiated cases.