Angiogenesis of hepatocellular carcinoma: An immunohistochemistry study

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

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.