Objectives Evaluation of the impact of discordant endometrial sampling on the prognosis of patients finally diagnosed with uterine papillary serous carcinoma (UPSC) and analysis of UPSC mutational profile.

Methods Retrospective cohort study comparing outcomes of patients with UPSC preoperatively diagnosed with endometrioid endometrial cancer (EEC) or UPSC. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 40 patients, using next generation sequencing.

Results 61 patients with UPSC on post-surgical, final pathology were included in the study. Prior to surgery, 15 were diagnosed with EEC (discordant) and 46 were correctly diagnosed with UPSC (concordant). After a median follow-up of 41.6 months [5.4–106.7], a preoperative diagnosis of EEC was associated with better 3-year progression-free survival (100% vs. 60.9%, P=0.003) and longer disease free interval (63.5 versus 15 months, P=0.026) compared to patients with an initial diagnosis of UPSC. Patients with a concordant diagnosis of UPSC were 5 times more likely to progress or die compared to those with a discordant EEC diagnosis (P=0.02, P=0.03, respectively ), and their tumors were associated with higher rates of TP53 (88.9% vs. 61.5%, P=0.04), and a lower rate of PTEN (14.8% vs. 38.5%, P=0.09)and ARID1A (3.7% vs. 23.1%, P=0.05) mutations.

Conclusions A pre-surgical diagnosis of EEC is associated with improved prognosis in patients with UPSC. Some histologically defined UPSC tumors contain endometrioid-like molecular characteristics that may confer a survival advantage.