title: Gene expression patterns related to vascular invasion and aggressive features in endometrial cancer.
abstract: The presence of tumor cells entering vascular channels is a prognostic marker for many cancers, including endometrial carcinoma. Vascular invasion is considered to be an early step in the metastatic process and important for the progress of malignant tumors. Here, we investigated the gene expression patterns related to vascular involvement in 57 primary endometrial cancers, using DNA microarray and quantitative PCR techniques. A vascular invasion signature of 18 genes was significantly associated with patient survival and clinicopathological phenotype. Vascular involvement was also related to gene sets for epithelial-mesenchymal transition, wound response, endothelial cells, and vascular endothelial growth factor (VEGF) activity. With immunohistochemical validation, both collagen 8 and matrix metalloproteinase 3 (MMP3) were associated with vascular invasion, whereas ANGPTL4 and IL-8 were associated with patient survival. Our findings indicate that vascular involvement within primary tumors is associated with gene expression profiles related to angiogenesis and epithelial-mesenchymal transition. These data could contribute to an improved understanding of potential targets for metastatic spread and may provide clinically important information for better management of endometrial cancer.
authors.affiliation: Section for Pathology, The Gade Institute, University of Bergen, Bergen, Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Mannelqvist
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stefansson
authors.forename: Geir
authors.initials: G
authors.lastname: Bredholt
authors.forename: Trond
authors.initials: T
authors.lastname: Hellem Bø
authors.forename: Anne M
authors.initials: AM
authors.lastname: Oyan
authors.forename: Inge
authors.initials: I
authors.lastname: Jonassen
authors.forename: Karl-Henning
authors.initials: KH
authors.lastname: Kalland
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D016000:Cluster Analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor