Patterns of gene expression related to vascular invasion and aggressive features in endometrial cancer

4703 Background: Vascular invasion is a marker of early metastatic spread and a prognostic factor for endometrial carcinomas. This histologic feature is also associated with activated angiogenesis and reduced vascular maturation, thus indicating that newly formed vessels are more vulnerable for tumor cell invasion that may result in metastasis. Aim: The aim of this study was to identify signatures of differentially expressed genes in endometrial carcinomas with vascular invasion as compared with cases without vascular involvement of tumor cells. Materials and methods: Fresh tumor tissues were prospectively collected from 57 patients treated for primary endometrial carcinoma. The tumors were analyzed with 21k Agilent oligonucleotide microarrays. Supervised analysis of the dataset was performed in order to identify differentially expressed genes between vessel invasive versus noninvasive tumors. Validation was done with quantitative reverse transcriptase PCR (qPCR) on 200 of the most differentially expressed genes. Results: Microarray based gene expression profiling followed by validation with qPCR identified genes related to vascular and extracellular matrix biology and whose expressions are significantly associated with vessel invasion. Gene set enrichment analysis (GSEA) gave significant enrichment in gene sets related to cell motility, wound response, angiogenesis and inflammation. Conclusion: We found several genes with significantly different expression between endometrial carcinomas with vascular invasion compared with those lacking vascular involvement, based upon microarray and qPCR studies. The most upregulated genes are related to invasiveness, angiogenesis and inflammation. Further studies on individual genes are performed on a large and independent series (n=288) of endometrial carcinomas.