EPV103/#218 Nuclear features allow for highly sensitive selection of endometrial carcinomas for P53 testing

Abstract

<h3>Objectives</h3> The World Health Organization endorses molecular subclassification of endometrial endometrioid carcinomas. Our objectives were to test the sensitivity of tumor morphology in capturing p53-abnormal (p53abn) cases and to model the impact of p53abn on changes to ESGO/ESTRO/ESP risk stratification. <h3>Methods</h3> 292 consecutive endometrial carcinoma resections received at Foothills Medical Centre, Calgary, Canada (2019–2021) were retrieved and assigned to ESGO risk groups without and with p53 status. Three pathologists reviewed representative H&amp;Es, predicted the p53 status, and indicated whether p53 immunohistochemistry would be ordered. Population-based survival for endometrial carcinomas diagnosed 2008–2016 in Alberta was obtained from the Alberta Cancer Registry. <h3>Results</h3> The cohort consisted mostly of grade 1/2 endometrioid carcinomas (EEC12; N=218, 74.6%). 152 EEC12 (52.1% overall) were stage IA and 147 (50.3%) were low-risk by ESGO. The overall prevalence of p53abn and subclonal p53 was 14.5% and 8.3%. The average sensitivity of predicting p53abn among observers was 83.6% and observers requested p53 immunohistochemistry on 39.4% with a sensitivity of 98.5% to detect p53abn (99.6% negative predictive value). Cytologic features including tumor giant cells, smudged chromatin, cherry-red/macronucleoli, and atypical mitoses accurately predicted p53abn. In 7/292, p53abn upgraded ESGO risk groups (2 to intermediate-risk, 5 to high-risk). EEC12/stage IA patients had an excellent cause-specific 5-year survival of 98.5%. <h3>Conclusions</h3> Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC12/stage IA.