title: Vascular endothelial growth factor receptor 2 expression in non-tumorous cirrhotic liver is higher when hepatoma is beyond Milan criteria.
abstract: Hepatocellular carcinoma (HCC) is a highly vascular tumor. Angiogenesis in HCC is mediated at least in part by vascular endothelial growth factor (VEGF), which is expressed in HCC and surrounding cirrhotic tissue. VEGF mediates its angiogenic effects through multiple receptors including VEGF receptor 2 (VEGFr2, KDR/FLK-1), The distribution and clinical significance of VEGFr2 expression in HCC and cirrhotic liver in the setting of liver transplantation have not been tissue site specific evaluated. Immunohistochemical staining for VEGFr2 was performed in 78 liver explants from patients with HCC undergoing liver transplantation. VEGFr2 levels in HCC were significantly increased compared to adjacent, nontumorous cirrhotic liver areas (P < 0.05). VEGFr2 levels were significantly higher in the veins and sinusoids of poorly differentiated tumors (P < 0.05). VEGFr2 levels in the tumors were not significantly different between patients within and beyond Milan criteria. However, VEGFr2 levels were significantly higher in the arteries of non-tumorous liver in patients beyond Milan criteria (P < 0.05). No significant association was observed between VEGFr2 levels and the presence of tumor vascular invasion or recurrence post transplantation. These findings suggest that VEGFr2 up-regulation is a feature of poor differentiation and tumor progression. Further investigation is needed to assess the value of angiogenesis modulation in preventing tumor formation and/or progression in cirrhotic patients.
authors.affiliation: Liver Transplantation, Cleveland Clinic, Cleveland, OH 44195, USA. aucejof@ccf.org
authors.forename: Federico
authors.initials: F
authors.lastname: Aucejo
authors.forename: Richard
authors.initials: R
authors.lastname: Kim
authors.forename: Nizar
authors.initials: N
authors.lastname: Zein
authors.forename: Cristiano
authors.initials: C
authors.lastname: Quintini
authors.forename: Teresa Diago
authors.initials: TD
authors.lastname: Uso
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Bijan
authors.initials: B
authors.lastname: Eghtesad
authors.forename: John
authors.initials: J
authors.lastname: Fung
authors.forename: Charles
authors.initials: C
authors.lastname: Miller
authors.forename: Lisa
authors.initials: L
authors.lastname: Yerian
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2