title: Morphologic changes and altered gene expression in an epithelioid hemangioendothelioma during a ten-year course of disease.
abstract: Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular neoplasm with unpredictable prognosis. We report on a patient suffering from a vascular neoplasm with primary manifestation in the skeleton and subsequent development of lesions of EHE in the spleen, liver and lung. Based on the assumption that involvement of visceral organs was due to metastatic spread, changes in clinical behavior, morphology, and proliferation index suggest malignant progression of the tumor. Analyzing the expression of genes known to be involved in the pathogenesis of vascular tumors, we found that the appearance of less differentiated tumor was paralleled by an accumulation of TP53 and murine double minute-2 (MDM-2) protein, decreased caveolin-1 (CAV-1) expression, and increased vascular endothelial growth factor (VEGF) expression. Mutations of the von-Hippel-Lindau-tumor-suppressor-gene (VHL) were excluded as mechanism of VEGF upregulation. Therefore, we propose that the expression of TP53, MDM-2, CAV-1 and VEGF as a marker of biologic behavior be verified in a larger case study of EHE.
authors.affiliation: Department of Pathology, University Hospital, Zurich, Switzerland.
authors.forename: Jean-Philippe P
authors.initials: JP
authors.lastname: Theurillat
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Vavricka
authors.forename: Philip
authors.initials: P
authors.lastname: Went
authors.forename: Dominik
authors.initials: D
authors.lastname: Weishaupt
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Christa
authors.initials: C
authors.lastname: Leonard-Meier
authors.forename: Esther B
authors.initials: EB
authors.lastname: Bachli
mesh_terms: D029681:Arabidopsis Proteins / Q000502:physiology; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018323:Hemangioendothelioma, Epithelioid / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008875:Middle Aged; D009687:Nuclear Proteins; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D013160:Splenic Neoplasms / Q000556:secondary; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D029681:Arabidopsis Proteins; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C423903:PHOT2 protein, Arabidopsis; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human