Two-Antibody Staining Method, A Cost-Saving Strategy for Universal Lynch Syndrome Screening in Endometrial Cancers

Objective: Lynch syndrome is an autosomal dominant disorder that increases the risk of cancers in many sites. In women, endometrial cancer is often a sentinel tumor and thus immunohistochemistry for mismatch repair (MMR) proteins MLH1, MSH2, MSH6 and PMS2 is encouraged as a screening test. To reduce cost, staining for only 2 MMR proteins PMS2 and MSH6 has been proposed. This study aimed to determine whether a 2-antibody staining test is enough to screen for Lynch syndrome in endometrial cancer patients. Materials and Methods: Cases of endometrial carcinoma with immunohistochemistry for 4 MMR proteins were reviewed. Results of immunohistochemistry screening were compared between all four antibodies and only two (PMS2 and MSH6) antibodies. Results: Loss of expression of any MMR proteins was detected in 51 out of 203 cases (25.12%). Twenty-three cases (45%) showed loss of MLH1 and PMS2; 13 cases (25%) showed loss of MSH2 and MSH6; five cases (10%) showed loss of MSH6; seven cases (14%) showed loss of PMS2 and three cases (6%) showed loss of MSH2. The 2-antibody method detected 48 cases (94%) with a MMR deficiency but failed to detect three cases (6%) with an isolate loss of MSH2. The screening results from the 2-antibody method are 98.5% (200/203) in accordance with the original 4-antibody method. Conclusion: The 2-antibody method is a quite effective option to screen for Lynch syndrome in endometrial cancers. However, MSH2 mutations may be missed in a few cases.