Impact of lower uterine segment involvement in type II endometrial cancer and the unique mutational profile of serous tumors

Objective: Evaluation of the impact of lower uterine segment involvement (LUSI) in type II endometrial cancer, and mutational profile of uterine papillary serous carcinomas (UPSC). Methods: Retrospective cohort study comparing patients with type II endometrial cancer with LUSI to patients without LUSI. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 42 patients with UPSC using next generation sequencing. Results: 83 patients with type II endometrial cancer were included in the study, of these, LUSI was diagnosed in 31.3%. During a median follow-up of 45.5 months, patients with LUSI developed more local and distant recurrences (local: 19.2% vs. 3.5%, P = .03; distant: 50% vs. 17.5%, P = .004) and progression events (73.1% vs. 26.3%, P < .001), with shorter mean progression-free survival (16 months compared to 26.5 months, P < .01). In a multivariate analysis, LUSI was the only significant pathological factor, associated with a 2.9-fold increase in the risk of progression (P = .007), and a 2.6-fold increase in the risk of death (P = .02). In the subgroup of patients with UPSC, mutations were identified in 54 genes, including TP53 (80%), PPP2R1A (40%), and PTEN (22.5%). Frequent mutations in the PTEN-PI3K-AKT signaling pathway were found in patients with tumor in the upper uterine segment only (P = .04), with PTEN being mutated in 29% of the samples (P = .07). Conclusion: Type II endometrial cancers presenting in the LUS have a significantly worse prognosis and this might be associated with a unique mutational profile. Keywords: Lower uterine segment, Uterine papillary serous carcinoma, Type II endometrial cancer, Sequencing, Gene analysis, PTEN mutatio

Additional file 1: Figure S1. of Chemotherapy reduces PARP1 in cancers of the ovary: implications for future clinical trials involving PARP inhibitors

PARP1 antibody validation. (A) Western blot of PARP1 and actin were performed on OVCAR8 cells infected with shRNA control or directed against PARP1. (B) The same cells used in (A) were paraffin-embedded and IHC staining against PARP1 was performed using the same antibody as in (A). The antibody shows high specificity and sensitivity for PARP1 protein in both techniques. (TIFF 1130 kb