High vascular endothelial growth factor (VEGF) expression in chemically-induced hepatic microcancers in mice.
OBJECTIVE
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.
Turlin
Bruno
B
Laboratory of Pathology, University Hospital Pontchaillou, 2 rue Henri Le Guilloux, 35033 Rennes Cedex, France. bruno.turlin@chu-rennes.fr
Le Quilleuc
Danielle
D
Leroyer
Patricia
P
Brissot
Pierre
P
Deugnier
Yves
Y
Loréal
Olivier
O
D000477:Alkylating Agents; D000818:Animals; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D019190:Iron Overload / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000477:Alkylating Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004052:Diethylnitrosamine