Analysis of Angiogenesis-Related Gene Expression Reveals a Profile with Prognostic Implications in Endometrioid Endometrial Carcinoma
Marta Mendiola, Andres Redondo, Javier de Santiago, Alicia Hernandez, Elia Perez-Fernandez, Maria Miguel-Martin, Esther Diaz, Jorge Barriuso, Victoria Heredia, Laura Yebenes, Jaime Feliu, David Hardisson. Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain; La Paz University Hospital, Madrid, Spain
Background: Endometrial cancer is the most common gynecologic malignancy in developed countries but little is known about the underlying mechanisms of tumor progression. Endometrioid adenocarcinoma (EAC) is the most frequent subtype and account for more than 80% of all endometrial adenocarcinomas. EAC tend to present as low grade, early stage tumors with good outcomes, often cured with surgery alone. However, approximately 15% of women with EAC will present with advanced FIGO stage and have a shorter 5-year survival rate. Enhanced tumor angiogenesis regulates the progression of endometrioid carcinomas. We have been focused on a selected group of genes related to this process in an attempt to identify a gene expression profile useful as prognostic marker for overall survival in EAC.
Design: 61 patients with EAC were included in this study. RNAs were collected from formalin-fixed paraffin-embedded samples. Specific TaqMan Gene Expression assays for 82 genes were selected and gene expression was determined by qRT-PCR with TaqMan Low Density Arrays (Applied Biosystems). We applied a normalization factor based on the geometric mean of 8 housekeeping genes, selected by Genorm Software. A logistic regression analysis was used to build multiple models based on the combination of significant genes selected by the Akaike Information Criterion. The accuracy of the model was determined by using the receiver operating characteristics (ROC). SAS 9.1 and SPSS packages were used for statistical tests.
Results: The mean overall survival was 152 months. We generated a predictive model based on the expression of 5 angiogenesis-related genes. According to the model, patients were divided into 2 risk groups, with 85% sensibility and 72% specificity. In a multivariate analysis including clinical variables the model was independently associated with overall survival.
Conclusions: These preliminary data support the relation of the angiogenic process with the prognosis of endometrioid endometrial carcinomas. Once validated, this 5-gene expression profile could be clinically useful for stratifying patients according to the risk of tumor progression and outcome.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 240, Tuesday Morning