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2022-RA-1479-ESGO Sex hormone receptor expression, MSH2 and MSH6 loss, but not β-catenin nuclear translocation, is concordant between synchronous endometrial and ovarian carcinomas
  1. Emily Southworth,
  2. Ian Croy,
  3. Michael Churchman,
  4. Charlie Gourley and
  5. CS Herrington
  1. Cancer Research UK Scotland Centre, The Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK


Introduction/Background Synchronous endometrial and ovarian carcinoma (SEOC) accounts for 10% of ovarian and 5% of endometrial cancers. SEOC tumours are staged separately but most demonstrate clonality. The ProMisE algorithm classifies endometrial carcinomas into p53 aberrant, mismatch repair deficient (MMRd), POLE mutant tumours and tumours of no specific molecular profile, up to ½ of which are CTNNB1 mutant (CTNNB1mut).

Methodology Formalin-fixed paraffin-embedded (FFPE) tissue was obtained from 34 patients with SEOC for haematoxylin and eosin (H&E) review, and immunohistochemistry (IHC). Progesterone receptor (PR) and estrogen receptor (ER) expression was scored between 0–300. Tumours were assessed for MMRd via MLH1, MSH2, MSH6 and PMS2 staining, and for presence of nuclear β-catenin (a surrogate marker of CTNNB1mut).

Results Tumours were of endometrioid (55/68, 80.9%), clear cell (4/68, 5.9%) and mixed endometrioid/clear cell (9/68, 13.2%) histology, and almost all were p53 wildtype (67/68). Neither ER (p = 0.15) nor PR (p = 0.98) expression was statistically significantly different between paired tumours. 9 of 34 cases were MMRd (26.5%); 4 and 2 cases had MSH2/MSH6 loss and MSH6 loss respectively, and this was conserved between the paired endometrial and ovarian tumours. 16 of 34 cases (47.1%) exhibited nuclear β-catenin staining of which only 6 had conserved presence of nuclear staining between tumour sites.

Conclusion ER and PR expression, MSH2 and MSH6 loss, but not nuclear β-catenin, is concordant between paired SEOC tumours, suggesting that β-catenin function may differ between endometrial and ovarian carcinomas, even in the synchronous context. Conserved loss of MSH2 and/or MSH6 between paired tumours in a subset of cases suggests underlying Lynch syndrome. Whole exome sequencing is underway to investigate the mutational landscapes of tumours, including the mutation status of MMR genes and CTNNB1.

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