Immunohistochemical Assessment of Angiogenesis in Primary Hepatocellular Carcinoma

Adrian Saftoiu1, Tudorel Ciurea1, Monica Banita2, Claudia Georgescu3, Violeta Comanescu3, Ion Rogoveanu1, Florin Gorunescu4, Ion Georgescu5

1) Department of Internal Medicine, Division of Gastroenterology. 2) Department of Histology. 3) Department of Pathology. 4) Department of Statistics. 5) Department of Surgery, University of Medicine and Pharmacy Craiova


Background. Primary hepatocellular carcinoma (HCC) is charac­terized by the presence of angiogenesis, which is necessary for tumor growth, progression and distant metastasis. Vascular endothelial growth factor (VEGF) is clearly expressed in HCC, in variable degrees as a function of differentiation and vascularisation.

Aim. To assess angiogenesis in HCC, by means of immunohistochemical analysis of the ex­pres­sions of VEGF.

Method. Immunohisto­che­mical tech­niques were performed on the samples ob­tained by ultrasound-guided liver biopsies or intraoperative biopsies, in 32 pa­tients with HCC.

Results. Positive expression of VEGF was always observed in the extracellular matrix of portal tracts of the non-neoplastic or tumor areas (extra- and intra­nodu­lar areas of HCC patients). VEGF was not expressed inside the hepato­cytes of extranodular non-neoplastic areas of the patients with HCC. How­ever, we did find positive reactions for VEGF inside the tumor hepa­to­cytes in 34.38% of the HCC patients. The difference between VEGF expression for the patients with poor and undiffe­ren­tiated HCC as compared with moderate and well-differentiated HCC was statis­ti­cally sig­ni­ficant (P < 0.05).

Conclusion. Our study demonstrated an increased VEGF expression in tumor hepatocytes, which progressed with the dedifferentiation of HCC. VEGF expression was always present in the extracellular matrix, supporting the hypo­thesis of paracrine activation of VEGF at the level of tumor stroma. Consequently, increased VEGF expression might be respon­si­ble for the activation of angiogenesis in HCC.

Key words

Hepatocellular carcinoma - angiogenesis - vascular endothelial growth factor - immunohistochemistry