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. 2019 Mar 27;11(3):294-304.
doi: 10.4254/wjh.v11.i3.294.

Angiogenesis of hepatocellular carcinoma: An immunohistochemistry study

Decebal Fodor  1 , Ioan Jung  1 , Sabin Turdean  1 , Catalin Satala  1 , Simona Gurzu  1
Affiliations

Angiogenesis of hepatocellular carcinoma: An immunohistochemistry study

Decebal Fodor et al. World J Hepatol. .

Abstract

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

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

Methods: 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.

Results: 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.

Conclusion: 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: Angiogenesis; Antiangiogenic therapy; Endothelial area; Hepatocellular carcinoma.

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Conflict of interest statement

Conflict-of-interest statement: This is a retrospective study. No consent was necessary. Conflict-of-interest statement: None declared.

Figures

Figure 1
Figure 1
Angiogenic phenotype of hepatocellular carcinoma cells. A: Vascular endothelial growth factor (VEGF) A shows a low intensity (score 2+) in aggressive cases with vascular invasion; B: VEGF-A is well expressed (score 3+) in well differentiated carcinomas; C: Cyclooxygenase-2 (COX-2) presents low intensity (score 1+) in well-differentiated carcinomas; D: COX-2 becomes upregulated (score 3+) in dedifferentiated tumors.
Figure 2
Figure 2
Particular features of neoangiogenesis of hepatocellular carcinoma, revealed by CD31 stain. A: Endothelization of the cirrhotic synusoids; B: High endothelial area and immature vessels in the peri-cirrhotic tumor tissue; C: Rare mature vessels can be intratumorally seen, in cases developed in patients without cirrhosis. 20 x.
Figure 3
Figure 3
Particular features of neoangiogenesis of hepatocellular carcinoma, revealed by CD105 stain. A and B: High microvessels density of normal parenchyma, compared with tumor tissue; C: Mature activated neoformed vessels, in a G1 carcinoma; D: Mature vessels, in a G2 carcinoma; E: Low endothelial area, in a G3 carcinoma; F: Small neoformed vessels, in a case with high endothelial area.
See this image and copyright information in PMC

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