High vascular endothelial growth factor (VEGF) expression in chemically-induced hepatic microcancers in mice

Background/Aims: In experimental carcinogenesis microcancers are defined as foci of altered hepatocytes showing vascular invasion. Vascular endothelial growth factor (VEGF) could be involved in such vascular extension. The aim of our study was to evaluate the in situ VEGF expression in chemically-induced microcancers. Methods: Fourteen C3H male mice were submitted to a diethyl nitrosamine-induced carcinogenesis. Iron-dextran overload was performed in parallel in order to localize all iron-negative lesions. Animals were sacrificed at 24,39 and 52 weeks of age. Liver sections were histologically (haematoxylin eosin safron (HES), Orcein and Perls' stains) and immunohistochemically (VEGF) studied. Results: Microcancers represented 8% of 424 lesions that we found as compared to foci (35%), adenomas (51%), and overt cancers (6%). VEGF hepatocyte positivity was found in 74% of lesions, with a more frequent, intense, and homogenous expression in microcancers than in other lesions, especially at 24 and 39 weeks. Conclusions: In our model, we found a high VEGF expression in microcancer exhibiting progression in vessels. Early overexpression of VEGF, formerly named vascular permeating factor, could act as a permeability factor and favors the development of vascular breakdown in microcancers. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.