Immunohistochemistry for mismatch repair protein deficiency in endometrioid endometrial carcinoma yields equivalent results when performed on endometrial biopsy/curettage or hysterectomy specimens.

Objective: Universal screening of endometrial cancer (EC) for Lynch syndrome (LS) has been increasingly implemented in the past five to ten years. Most pathologists initiate screening with immunohistochemistry (IHC) for mismatch repair proteins (MMRPs), using either pre-surgical samplings (endometrial biopsy or curettage, EMB/C) or hysterectomy specimens. We report a systematic assessment of the equivalence of IHC for LS screening on EMB/C versus hysterectomy specimens.

Methods: We identified 99 patients diagnosed with endometrioid EC and performed IHC for MMRPs MLH1, MSH2, MSH6, and PMS2 on their diagnostic EMB/C and paired hysterectomy specimen. Each specimen was scored as MMRP-retained or MMRP-deficient.

Results: Ninety-one EMB/Cs had carcinoma, while 8 EMB/Cs showed only complex atypical hyperplasia (CAH). Carcinoma was identified in all 99 hysterectomy specimens. Considering all 99 patients tested, concordance of MMRP expression pattern between EMB/C and paired hysterectomy specimen was 100%. Sixty-nine cases retained all four MMRPs, while 30 were MMRP deficient (26 MLH1- and PMS2-deficient, 3 MSH2- and MSH6-deficient, 1 PMS2-deficient).

Conclusions: In screening for LS in EC, IHC for MMRPs can be performed with identical accuracy on either EMB/C or hysterectomy specimens. Routine testing of diagnostic EMB/Cs may lead to earlier detection of MMRP deficiency, with improved patient uptake of genetic counseling and potential for earlier identification of immunotherapy candidates. Furthermore, reliable IHC-based LS screening performed on EMB/C can guide patient management and genetic counseling in patients unable to undergo hysterectomy.