Clinical translation of MMR protein expression analysis in uterine aspirates from Lynch syndrome women

Nuria Dueñas1, August Vidal2, Matilde Navarro1, Julia Canet1, Monica Salinas1, Laura Costas3, Jordi Ponce4, Xavier Matias-Guiu 2, Paula Peremiquel3, Sergi Fernandez4, Marta Pineda1, Gabriel Capellá1, Joan Brunet1,5

1Hereditary Cancer Program, Catalan Institute of Oncology-IDIBELL, ONCOBELL, Hospitalet de Llobregat, Spain. 2Department of Pathology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain. 3Unit of Molecular Epidemiology and Genetics in Infections and Cancer, Catalan Institute of Oncology-IDIBELL, Hospitalet de Llobregat, Spain. 4Department of Gynaecology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain. 5Hereditary Cancer Program, Catalan Institute of Oncology-IDBIGI, Girona, Spain



Previous studies have shown the presence of mismatch repair (MMR)-deficient glands in normal endometrium (NE) from Lynch syndrome (LS) female carriers.1-4 Its role as predictor of cancer development is unknown.

Our objective was to assess the usefulness of MMR immunohistochemistry (IHC) in the pathological analysis of endometrial aspirates for the diagnosis of endometrial cancer (EC) or preneoplastic lesions.



– Histological characterisation and MMR protein expression in endometrial aspirates from 33 LS women included in a prospective study (SCREENWIDE).5

– Bibliographic review of related studies



  1. Exploratory analysis of our series:

– 34 LS aspirates: median age 42.9y.

2 IHC-d EC:

54y, MLH1, asymptomatic, suspicious TVUS.

63y, PMS2, asymptomatic, normal TVUS.

1 IHC-d complex hyperplasia with atypia (CHA): 41y, MSH6, normal TVUS.

1 IHC-d complex hyperplasia (CH): 33y, MSH2, normal TVUS.

6 IHC-d NE: median age 38.7y. 1 MLH1, 1 MSH2, 4 MSH6, normal TVUS.

24 IHC proficient NE: median age 40.7y. 13 MLH1, 3 MSH2, 5 MSH6, 3 PMS2, TVUS: 1 endometrial polyp, 4 myomas, 18 normal.

  1. Bibliographic review: (Table 1)

– MMR-deficiency is usually identified in NE samples. IHC patterns are the expected by the underlying germline mutation.

– MSI-H and IHC-d increase as NE evolves to preneoplastic lesions and EC. IHC-d (biallelic loss) is detected before MSI-H (microsatellites mutation accumulation).



– CH and CHA, precursor EC lesions, show IHC-d and MSI-H in a high percentage.

– More data is required to assess the role of MMR-deficient repair as a risk indicator for EC and preneoplastic lesions.

Abstract references

  1. Sutter C, Dallenbach-Hellweg G, Schmidt D, et al. Molecular analysis of endometrial hyperplasia in HNPCC-suspicious patients may predict progression to endometrial carcinoma. Int J Gynecol Pathol. 2004;23(1):18-25. doi:10.1097/01.pqp.0000101085.35393.
  2. Nieminen TT, Gylling A, Abdel-Rahman WM, et al. Molecular analysis of endometrial tumorigenesis: importance of complex hyperplasia regardless of atypia. Clin Cancer Res. 2009;15(18):5772-5783. doi:10.1158/1078-0432.CCR-09-0506.
  3. Bats AS, Blons H, Narjoz C, et al. Microsatellite instability analysis in uterine cavity washings to detect endometrial càncer in Lynch syndrome. Anticancer Res. 2014;34(6):3211-3215.
  4. Niskakoski A, Pasanen A, Lassus H, et al. Molecular changes precedint endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance. Mod Pathol. 2018;31(8):1291-1301. doi:10.1038/s41379-018-0044-4.
  5. Costas L, Frias-Gomez J, Guardiola M, et al. New perspectives on screening and early detection of endometrial càncer. Int J Cancer. 2019. doi:10.1002/ijc.32514.