PT  - JOURNAL ARTICLE
AU  - S Kim
AU  - A Tone
AU  - A Pollett
AU  - R Kim
AU  - M Cesari
AU  - B Clarke
AU  - L Eiriksson
AU  - T Hart
AU  - S Holter
AU  - A Lytwyn
AU  - M Maganti
AU  - L Oldfield
AU  - T Pugh
AU  - S Gallinger
AU  - M Bernardini
AU  - A Oza
AU  - V Dube
AU  - J Lerner-Ellis
AU  - E Van de Laar
AU  - D Vicus
AU  - S Ferguson
TI  - 5 Understanding the clinical implication of mismatch repair deficiency in endometrioid endometrial cancer through a prospective study
AID  - 10.1136/ijgc-2020-IGCS.5
DP  - 2020 Nov 01
TA  - International Journal of Gynecologic Cancer
PG  - A4--A4
VI  - 30
IP  - Suppl 3
4099  - http://ijgc.bmj.com/content/30/Suppl_3/A4.short
4100  - http://ijgc.bmj.com/content/30/Suppl_3/A4.full
SO  - Int J Gynecol Cancer2020 Nov 01; 30
AB  - Objectives Findings on impact of mismatch repair deficiency (MMRd) on patient outcomes in endometrial cancer (EC) have been inconsistent to date. The objective of this study was to compare oncologic outcomes between MMRd and MMR-intact (MMRi) endometrioid EC (EEC).Methods Between 2015–2018, we prospectively recruited 668 EC cases from three cancer centers in Ontario, Canada. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinicopathological, treatment and survival data were compared between MMRd and MMRi cases.Results Out of 668, there were 496 EEC (74%), with 347 MMRi (70%) and 149 MMRd (30%) cases treated with surgery and with complete follow-up information. Median follow-up was 16.8 months (6–96 months). MMRd tumors tended to be grade 2 or 3 (56% vs. 29%, p<0.001), with propensity for lymphovascular space invasion (LVSI) (29% vs. 17%, p=0.004) and received more adjuvant treatment (45% vs. 33%, p=0.03). This group also had significantly lower 3-year RFS (78% vs. 89%, p=0.02) although there was no difference in OS (p=0.91). MLH1/PMS2 deficient tumors had the lowest 3-year RFS compared to intact and other MMRd tumors (76% vs. 89% vs 87%, p=0.02). After adjusting for age, stage, grade, use of adjuvant treatment, and LVSI status, MLH1/PMS2 deficiency was still associated with the lowest RFS (p=0.05).Abstract 5 Figure 1 Comparison of recurrence free survival between mismatch repair deficient (MMRd) and mismatch repair intact (MMRi) endometrioid endometrial cancersConclusions MLH1/PMS2 deficient EECs exhibit more aggressive features compared to other MMRd and MMRi cases, with worse RFS. This may indicate an inherent difference in tumor biology, suggesting the importance of individualized management based on tumor’s molecular phenotype.