The prognostic value of molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly due to the fact that different studies have used mixtures of histotypes, FIGO stages and different non-standardized non-automated methods. We have evaluated the prognostic value of classical prognostic factors, molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in a population-based cohort of FIGO stage I endometrial endometrioid adenocarcinomas. Curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients were reviewed. Clinical information, including follow-up, was obtained from the patients' charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections and molecular biomarkers using tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan-Meier method) and multivariate (Cox model) survival analysis was performed. With median follow-up of 66 months (1-209), 14 (6%) patients developed metastases. Age, microsatellite instability, molecular biomarkers (p16, p21, p27, p53 and survivin) and morphometric mean shortest nuclear axis had prognostic value. With multivariate analysis, combined survivin, p21 and microsatellite instability overshadowed all other variables. Patients in which any of these features had favorable values had an excellent prognosis, in contrast to those with either high survivin or low p21 (97 vs 78% survival, Po0.0001, hazard ratio ¼ 7.8). Combined high survivin and low p21 values and microsatellite instability high identified a small subgroup with an especially poor prognosis (survival rate 57%, P ¼ 0.01, hazard ratio ¼ 5.6). We conclude that low p21 and high survivin expression are poor prognosis indicators in FIGO stage I endometrial endometrioid adenocarcinoma, especially when high microsatellite instability occurs. Modern Pathology (2011Pathology ( ) 24, 1262Pathology ( -1271 doi:10.1038/modpathol.2011 published online 6 May 2011 Keywords: endometrial cancer; FIGO I; microsatellite instability; prognostic; p21; survivin Endometrial carcinoma is the most frequent gynecological cancer. The disease-related death rate in FIGO stage II-IV is high (20-80% and higher), while in the 'favorable' early stage FIGO I, the death rate ranges from 5 to 15%, 1,2 which has been stable for decades.3 This prompts the search of other prognostic indicators to enable a more accurate triaging
