Abstract

VEGF (vascular endothelial growth factor) and the receptor for VEGF- Flk-1 (fetal liver kinase 1) are important players of normal and pathologic angiogenesis. Also, it was proved that they are involved in tumor progression and metastasis in many tumors types by overexpression in cancer cells. Liver malignances and premalignant lesions represent controversial issues concerning VEGF and VEGFR2 (vascular endothelial growth factor receptor 2) expression and their potential involvement in the progression of inflammatory and cirrhotic lesions and also in malignant transformation is virtually unknown. The aim of this work was to describe the differentiate expression and distribution of VEGF and VEGFR2 in chronic hepatitis and liver cirrhosis, and according to these findings to better characterize the molecular profiling of liver disease with malignant transformation potential. We investigated 20 cases with chronic hepatitis and cirrhosis on specimens taken during surgery. Immunohistochemistry was performed in all cases for VEGF, VEGFR2, and FVIII related antigen (Von Willebrand factor). We found significant correlation between HAI (histological activity index) value, VEGF and VEGFR2 expression and factor FVIII related antigen in central part of specimens with chronic hepatitis. Liver cirrhosis lacks this correlation. Our findings suggested that VEGF dependent angiogenesis is more active in chronic hepatitis in the center of the lesion compared with cirrhosis where MVD (microvessel density) is higher at the periphery of the nodules. We hypothesize that the involvement of VEGF and VEGFR2 complex in development of chronic hepatitis and liver cirrhosis could be considered for the use of anti VEGF antibodies as adjuvant therapy in early stages of these diseases.

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