Despite the known association between MMR loss and Lynch syndrome (LS), data on EC is sparse; the degree of association is unknown as are the implications in term of prognosis and survival.
Descriptive analysis of 396 tumour samples of patients (pts), treated between Jan 2012 to Jan 2018, MMR proteins were tested by immunohistochemistry. Median follow up time was 23.2 months. Tumours with loss of at least one protein were considered MMR(d). Patient characteristics were recorded from our electronic records. Survival was assessed by Kaplan Mayer and log-rank test.
29% (114) tumours were deemed MMRd. Predominant histological subtype was endometrioid, high grade serous (HGS) including carcinosarcoma and clear cell. The most common somatic loss was MLH1-PMS2 (69%). 41% (47 pts) underwent germline testing for LS, 13pts (27.6%) were diagnosed with LS, association rate was PMS2 (100%), MSH6 (87.5%) and MSH2 MHS6 (40%). Our data suggest a non-significant differential survival between MMR proficient (p) and MMRd tumours (OS 116 months vs 82.9 months p0.756).
Almost 30% of unselected EC pts have somatic loss MMR proteins; 27% of patients have a germline mutation that is more commonly associated with loss of PMS2, MSH6 and MSH2 MSH6, and endometrioid histology. Differences in survival between MMRp and MMRd tumours need to be further investigated. Patient characteristicsMMRd(n = 114) LS (n = 13) Age of diagnosis 65 (41 – 87) 55 (41 – 84) BMI 31.35 (18.4 – 58.3) 28 (19.3 – 31.1) Histological subtype Endometrioid HGS/Carcinosarcoma Clear cell Others 86 (75%) 13 (12%) 3 (3%) 12 (10%) 10 (77%) 3 (23%) Rate of relapse/progression 31% (36) 23% (3) Localization of relapse/progression Systemic Loco-regional Vagina vault 36% (13) 50% (18) 14% (5) 100% Mortality rate 16% (18) 8% (1) Mean PFS 52.27 (43 – 61.5) 50 (35.7 – 64.5) Mean OS 82.9 (66.8 – 99) 72 (56.5 – 87.6)
Royal Marsden NHS Foundation Trust.
Has not received any funding.
All authors have declared no conflicts of interest.