Obstet Gynecol Sci.  2023 Nov;66(6):537-544. 10.5468/ogs.23124.

A simplified two-marker immunohistochemistry strategy for Lynch syndrome screening in endometrial cancer patients

  • 1Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
  • 2Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
  • 3Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
  • 4Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
  • 5Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea


To examine the efficacy of MSH6 and PMS2 immunohistochemistry (IHC) as a screening method for Lynch syndrome in endometrial cancer patients.
Through multidisciplinary discussions, an institutional MSH6 and PMS2 IHC-initiated cascade test (MSH6, PMS2 IHC→microsatellite instability [MSI] assay→germline mismatch repair [MMR] gene sequencing) was developed to screen for Lynch syndrome in endometrial cancer patients. Testing was performed on a consecutive cohort of 218 newly diagnosed endometrial cancer patients who underwent surgery at a tertiary hospital in the Republic of Korea between August 2018 and December 2020. The number of MMR deficiencies (MSH6 or PMS2 loss in IHC) and results of subsequent tests (MSI assay and germline MMR gene sequencing) were examined.
MMR deficiency was detected in 52 of the 218 patients (24.0%). Among these 52 patients, 34 (65.0%) underwent MSI testing, of which 31 (91.0%) exhibited high MSI. Of the 31 patients with MSI-high status, 15 (48.0%) underwent germline MMR gene sequencing. Subsequently, Lynch syndrome was diagnosed in five patients (33.0%).
Lynch syndrome screening using MSH6 and PMS2 IHC-initiated cascade testing is a viable strategy in the management of endometrial cancer. A simplified strategy (MSH6 and PMS2 IHC→germline MMR gene sequencing) was proposed because most women with MMR deficiencies exhibited high MSI.


Lynch syndrome II; Mass screening; G-T mismatch-binding protein; Immunohistochemistry


  • Fig. 1 Lynch syndrome screening guideline for endometrial cancer patients. IHC, immunohistochemistry; MSI, microsatellite instability; MSS, microsatellite stable; MSI-L, microsatellite instability-low; MSI-H, microsatellite instability-high; MMR, mismatc repair gene.

  • Fig. 2 Representative immunohistochemical images of MSH6 and PMS2 protein expression. (A) Intact MSH6 expression. Complete loss of MSH6 (B) and PMS2 (C) expression (×100 magnification).

  • Fig. 3 Updated guideline for Lynch syndrome screening. IHC, immunohistochemistry; MMR, mismatch repair gene.



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