The prognostic value of molecular biomarkers , microsatellite instability, DNA ploidy, and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly because different studies have used mixtures of histotypes, FIGO stages, and varying nonstandardized non-automated methods. The authors conducted a study in which they 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. They reviewed curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients and obtained clinical information, including followup, from patients’ charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections, and molecular biomarkers in tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan-Meier method) and multivariate (Cox model) survival analysis was performed. With a median followup of 66 months (one to 209 months), 14 (six percent) 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 whom any of these variables had favorable values had an excellent prognosis, in contrast to those with high survivin or low p21 values (97 percent versus 78 percent survival; P<.0001; hazard ratio, 7.8). Combined high survivin and low p21 values and high microsatellite instability identified a small subgroup with an especially poor prognosis (survival rate, 57 percent; P=.01; hazard ratio, 5.6). The authors concluded that low p21 and high survivin expression are indicators of poor prognosis in FIGO stage I endometrial endometrioid adenocarcinoma, especially when high microsatellite instability occurs.