Improving genetic testing following abnormal mismatch repair immunohistochemistry results in endometrial cancer

Although universal mismatch repair (MMR) immunohistochemistry (IHC) in endometrial cancer began at our institution in July 2015, not all eligible patients were referred for genetic testing (GT). In April 2017, genetic counselors obtained IHC data and contacted physicians to approve genetic counseling referrals (GCRs) for Lynch Syndrome (LS) in eligible patients. We assessed if this protocol increased frequency of GCRs and GT in patients with abnormal MMR IHC.

We retrospectively (7/2015-5/2022) identified patients with abnormal MMR IHC at a large urban hospital. GCRs and GT were compared between cases from 7/2015-4/2017 (pre-protocol) and 5/2017-5/2022 (post-protocol) with chi-square and Fisher's exact tests.

Of 794 patients with IHC testing, 177 (22.3%) had abnormal MMR results with 46 (26.0%) meeting criteria for LS screening with GT. Of 46 patients, 16 (34.8%) were identified prior to and 30 (65.2%) after the protocol initiation. GCRs significantly increased from 11/16 (68.8%) to 29/30 (96.7%) in the pre-protocol versus post-protocol groups, p = 0.02. There was no statistically significant difference in GT between groups (10/16, 62.5% vs 26/30, 86.7%, p = 0.07). Of 36 patients who underwent GT, 16 (44.4%) had LS: MSH6, 9; MSH2, 4; PMS2, 2; MLH1, 1.

Increased frequency of GCRs was observed following the change in protocol, which is important as LS screening has clinical implications for patients and their families. Despite this additional effort, approximately 15% who met criteria did not undergo GT; further efforts such as universal germline testing in patients with endometrial cancer should be considered.