597P Endometrial carcinoma and mismatch repair deficiency: Clinical association and universal screening for Lynch syndrome

Abstract

Endometrial carcinoma (EC) is characterised by a high rate of DNA Mismatch Repair deficiency (dMMR). Testing for dMMR might have implications for EC prognosis and is part of Universal Screening (US) for Lynch syndrome (LS) diagnosis. However, this is not widely implemented yet, and LS is still underdiagnosed. For these reasons, we aimed to evaluate dMMR prevalence, its association with clinicopathological variables and its role for LS diagnosis for EC patients. This is a monocentric retrospective study on 368 consecutive EC cases (stages I-IV). From 2013 to 2020 they underwent surgery and immunohistochemistry (IHC) analysis for dMMR. We collected age, date of surgery, tumor histotype, grading, FIGO stage at diagnosis, lymphovascular invasion (LVSI), and survival status. We then assessed the proportion of dMMR patients on the entire cohort. Major outcome were OS and RFS in the dMMR patients compared to MMR proficient cases (pMMR). Among the dMMR cases, we reported those who underwent genetic testing and had LS. dMMR was found in 91/368 EC patients (25%). 84 had endometroid histotype, 7 other histotypes (92% vs 8% p= 0.010), 50 had G2 nuclear grading vs 19 G1 and 22 G3 (55% vs 21% vs 24%; p=0.005). As compared to pMMR at a 4-year follow-up an unfavorable trend in OS and RFS was observed for patients with dMMR (4 y OS 82% vs 74% p=0.115, 4 y RFS 70% vs 54% p-value=0.153). In multivariate analysis, age (p<0.001), histotype and grade (p<0.001), stage (p=0.003) and LVSI (p=0.010) were independently associated to OS. dMMR only showed a trend in worse OS (p=0.10). Among the 91 patients with dMMR, only 5 underwent genetic counseling (GC)(6.6%): LS was diagnosed in 1 patient (20%) with loss of MSH2/MSH6 expression. This is the largest Italian cohort of US for LS. dMMR prevalence was 25%, mainly associated with endometrioid type, G2 grading and a worse 4 y OS, as compared to pMMR cases, consistent with the literature. Unfortunately, oncologists' compliance with US for LS is still very poor, with a 6.6% GC referral. This should be implemented according to international guidelines, to increase LS diagnosis, reduce mortality in relatives and incidence of second cancers in survived patients.