Clinicopathological and molecular landscape of lynch-associated endometrial carcinoma undergoing surveillance: a retrospective single-centre cohort study

Introduction/Background:
Lynch syndrome (LS) is the leading hereditary cause of endometrial carcinoma (EC), characterised by mismatch-repair (MMR) deficiency and typically presenting at an early stage. While initial prognosis is favourable, the long-term behaviour and metastatic potential of LS-associated EC remain poorly characterised. At our centre, women >35 years with confirmed LS have been offered annual hysteroscopic surveillance with endometrial sampling since 2007. This study describes the clinicopathological, and molecular profiles of genetically confirmed LS-associated EC managed at a tertiary UK referral centre.

Methods:
This retrospective consecutive series study was conducted on 14 consecutive genetically confirmed LS patients undergoing surveillance, diagnosed with EC between September 2008 and March 2024. Demographic, histopathological, and molecular variables were collected from patient records, including FIGO stage, tumour grade, MMR gene variant, MMR immunohistochemistry profile, treatment, and clinical outcome.

Results:
Median age at EC diagnosis was 41 years (range 31-57). Most cases (86%) were FIGO IA (12/14), with one IB and one IIIB. Histology was uniformly endometrioid: Grade 1 (71%), Grade 2 (29%), none Grade 3. Pathogenic variants involved were MSH2 (57%) and MLH1 (43%). All tumours were MMR-deficient, p53 wild-type, with 86% ER-positive. All patients underwent laparoscopic/robotic hysterectomy ± bilateral-salpingo-oophorectomy ± sentinel-node sampling; one (7%) with stage IIIB received adjuvant pelvic radiation and Carboplatin-Paclitaxel chemotherapy. After a median follow-up of 8 years (range <1-17), 93% remained disease-free. One patient (Stage IA, Grade 1 endometrioid adenocarcinoma with negative sentinel node on ultrastaging) developed a late metastatic relapse 8 years post-hysterectomy, treated palliatively.

Conclusion:
LS-associated EC at our centre was predominantly diagnosed at early-stage and low-grade, with excellent survival, possibly reflecting proactive early-stage detection through structured hysteroscopic surveillance.

#254
Part of an 'ePoster Session'