Abstract 4253
Background
Endometrial cancer (EC) is the most common gynaecological malignancy worldwide. The TCGA data suggested up to 30% of EC pts have a MMR deficient (MMRd) tumours, however the exact concordance of this with the presence of a germline mutation (Lynch syndrome) in an unselected population is unclear. Lynch-associated tumours appear to have a better prognosis, however the implications for prognosis and survival in all MMRd tumours are less known.
Methods
396 pts with primary endometrial cancer, treated at RMH were evaluated for MMR proteins by immunohistochemistry (IHC). Tumours with loss of at least one protein were considered MMRd, those with intact expression were MMR proficient (MMRp). Clinico-pathological characteristics and survival data was collected from electronic records. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan Meier and log-rank tests.
Results
Of 396 samples tested to date, 29% (114 pts) were MMRd. Frequencies of IHC MMR loss of expression were: MLH1/PMS2 loss: 80, MSH2/MSH6 loss: 10, MSH6 loss: 12, PMS2 loss: 9, other patterns: 3. Germline testing has been completed in 37% (42 pts) thus far; 14pts had a concordant germline mutation: MLH1 (2/25), MSH2 (3/7), MSH6 (7/8), PMS2 (2/2) respectively. Mean age varied significantly, at 66 yrs (MMRd), 65yrs (MMRp) and 58 yrs (Lynch mutation carriers, LS) p = 0.022: as did mean BMI: 33 (MMRd), 26 (LS) and 36 (MMRp), p = 0.023. Stage at diagnosis did not differ significantly between the groups but MMRd and LS patients were significantly more likely to have LVSI than MMRp (p = 0.01), and to be high EORTC risk (p = 0.006). OS for the entire cohort was 160mths (75-244.9) and PFS was 51.6mths (32.4-70.7). MMRd pts had a shorter OS (96.4mths, 95%CI 65.7 – 127) than MMRp (160mo, 54.9 – 265) and a shorter PFS median PFS 41.4mo (IC 95% 18.9– 64) vs 51.6mo (IC 95% 30- 72), p.021].
Conclusions
Almost one in three EC tumours are MMRd, with concordance between IHC loss and presence of a germline mutation varying by gene. Those with somatically derived MLH1/PMS2 loss may have a poorer prognosis, and as a group may potentially benefit from checkpoint inhibitors. Further exploration of the clinical correlations and outcome with MMR status is warranted.
Clinical trial identification
Legal entity responsible for the study
The Royal Marsden NHS Foundation Trust.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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