Vascular endothelial growth factor expression in hepatic epithelioid hemangioendothelioma: Implications for treatment and surgical management.
Epithelioid hemangioendothelioma (EHE) is a low-grade, malignant vascular tumor that most commonly presents within the liver. Patients with hepatic EHE are often candidates for liver transplantation as the disease is usually multifocal at diagnosis. Although these patients achieve excellent early outcomes post-transplant, there are very few data regarding tumor markers that can further direct chemotherapy in hepatic EHE to prevent recurrent disease. The purpose of this study was to analyze the expression of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors in hepatic EHE. Six patients with hepatic EHE were assessed for liver transplantation at our center. Pathology specimens of primary and recurrent EHE were analyzed by hematoxylin and eosin staining and by immunofluorescence for VEGF, fetal liver kinase 1 (Flk-1), and fms-related tyrosine kinase 1 (Flt-1) expression. Five patients underwent liver transplantation, and 1 patient underwent liver resection. Biopsy-proven recurrent EHE occurred in 3 patients. VEGF expression was present in 100% of the EHE specimens examined, whereas Flt-1 expression was present in only 1 sample, and Flk-1 was not observed in any of the specimens. In 1 patient with recurrent hepatic EHE post-liver transplantation, a progressive increase in the VEGF fluorescence intensity and distribution was observed. In conclusion, in this series, VEGF expression was observed in all hepatic EHE specimens analyzed. These data suggest that anti-VEGF chemotherapeutic agents will be of use in patients with hepatic EHE, particularly as a means of reducing the tumor volume prior to resection, as a means of treating unresectable or metastatic disease, or as an adjuvant therapy in the setting of liver transplantation.
Emamaullee
Juliet A
JA
Department of Surgery, University of Alberta, Edmonton, AB Canada AB T6G 2E1. juliete@ualberta.ca
Edgar
Ryan
R
Toso
Christian
C
Thiesen
Aducio
A
Bain
Vincent
V
Bigam
David
D
Kneteman
Norman
N
Shapiro
A M James
AM
D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D018572:Disease-Free Survival; D005260:Female; D018323:Hemangioendothelioma, Epithelioid / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2