Microsatellite instability and ploidy status define three categories with distinctive prognostic impact in endometrioid endometrial cancer

// Cristina Bilbao-Sieyro 1,2 , Raquel Ramirez-Moreno 1,2 , German Rodriguez-Gonzalez 1,2 , Orlando Falcon 1,3 , Laureano Leon 1,4 , Santiago Torres 2 , Leandro Fernandez 1,5 , Sergio Alonso 6 , Nicolas Diaz-Chico 1,2 , Manuel Perucho 6,7,8 and Juan Carlos Diaz-Chico 1,2 1 Cancer Research Institute of The Canary Islands (ICIC), Las Palmas de Gran Canaria, Canary Islands, Spain 2 Biochemistry, Molecular Biology and Physiology Department, Molecular and Translational Endocrinology Group, Institute for Biomedical and Health Research, Faculty of Health Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Canary Islands, Spain 3 Obstetrics and Gynecology Department, Hospital Universitario Materno-Insular de Canarias, Las Palmas de Gran Canaria, Canary Islands, Spain 4 Pathology Department, Hospital Universitario Materno-Insular de Canarias, Las Palmas de Gran Canaria, Canary Islands, Spain 5 Clinical Sciences Department, Molecular and Translational Endocrinology Group, Institute for Biomedical and Health Research, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Canary Islands, Spain 6 Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain 7 Sanford-Burnham Medical Research Institute (SBMRI), La Jolla, CA, USA 8 Institucio Catalana de Recerca i Estudis Avancats (ICREA), Passeig Lluis Companys 23, Barcelona, Spain Correspondence: Manuel Perucho, email: // Keywords : endometroid, endometrial cancer, microsatellite instability, aneuploidy, survival Received : June 19, 2014 Accepted : July 06, 2014 Published : July 08, 2014 Abstract Microsatellite instability (MSI) and aneuploidy are inversely related phenomena. We tested whether ploidy status influences the clinical impact of MSI in endometrioid endometrial cancer (EEC). We analyzed 167 EECs for MSI and ploidy. Tumors were classified in three categories according to MSI and ploidy status. Associations with clinicopathological and molecular variables, survival, and treatment response were assessed. All MSI tumors (23%) were scored as diploid, and 14% of microsatellite stable (MSS) tumors presented aneuploidy. MSI tumors associated with older age at diagnosis, non-obesity, high histological grade, and advanced surgical stage. MSS-aneuploid tumors also associated with higher grade and advanced stage. In multivariate survival analysis MSI did not influence disease-free survival (DFS) or cancer-specific survival (CSS). However, when just diploid tumors were considered for the analysis, MSI significantly contributed to worse DFS and CSS, and the same was observed for aneuploidy when MSS tumors were analyzed alone. In diploid tumors, a differential response to postoperative radiotherapy (RT) was observed according to MSI, since it predicted poor DFS and CSS in the multivariate analysis. We conclude that ploidy status influences the clinical impact of MSI in EEC. Among diploid tumors those with MSI have poor clinical outcome and respond worse to RT.