The Kaplan-Meier estimator was employed for survival analysis, and the generated curves were compared

with the log-rank test. The endpoint for the study was overall survival (OS). OS was defined as the time from sample collection to death or censoring. Censoring was defined as loss of follow-up GSK-3 inhibitor review or alive at the end of follow-up. Statistical significance was assumed when P ≤ .05. Cox proportional hazards regression analysis was used to identify the independent predictors of OS. Univariate predictors that are significant with a value of P ≤ .10 were entered into a step-wise multivariate model to identify those with independent prognostic information. For tumor heterogeneity evaluation, staining determination of at least three cores was required. Within the group of 364 patients, tumor heterogeneity was assessed for 310 to 355 (85.2-97.5%) cases, depending on the staining success of a given protein (Table W2). Global heterogeneity was assessed for 355 patients, as cases

with less than five assessed proteins were not considered in the context of global heterogeneity due to the lack of significant proportion of data. Graphical representation of tumor heterogeneity within this group is presented in Figure 1. Tumor heterogeneity of the studied proteins was compared

with selleck chemical tumor histology, grade, and stage as well as the presence of metastases (Table 2). Parameters such as menopausal status, age, obesity, or myometrial infiltration were not included in the table as these analyses yielded statistically insignificant results. Particularly strong correlation was found between TOP2A and CDKN2A heterogeneity and higher stage of the disease (P = .0002 and P = .0003, respectively). Most correlations with clinicopathologic data were observed for ESR1 heterogeneity that correlated with non-endometrioid mafosfamide tumors (P = .02), higher stage (P = .005), grade (P = .01), and the presence of metastases (P = .00001). No correlations were found between the studied parameters (histology, stage, grade, metastases) and the tumor heterogeneity of ERBB1, ERBB2, ERBB3, ERBB4, pAKT1, and TP53, thus these proteins were included in Table W3 only. Tumor heterogeneity of the studied proteins was compared with each other. Strong correlation was found between ESR1 and PGR heterogeneity (r = 0.30, P = .000002), ESR1 and RAD21 heterogeneity (r = 0.23, P = .0003), and pAKT1 and ERBB1 heterogeneity (r = 0.24, P = .0002). Protein heterogeneity of MYC, TOP2A, ESR1, and RAD21 correlated with shortened OS. The same trend was observed for ERBB4, RUNX1, and CDKN2A.