P2619 - Investigating Care Gaps Following Identification of Mismatch Repair Deficiency in Gastrointestinal Cancers

Matthew Yizong. Zhao, MD, Noam Harpaz, , Dana Zalkin, MD
Icahn School of Medicine at Mount Sinai, New York, NY

Introduction: Lynch syndrome (LS) is the most common hereditary cancer syndrome, and results from autosomal dominant mutations in DNA mismatch repair (MMR) genes. Although universal tumor-based screening for MMR deficiency is now recognized as the standard of care, follow-up of positive screening at our institution is not standardized. As part of an ongoing quality improvement initiative, we evaluated care gaps following positive tumor-based screening for LS.

Methods: We performed a retrospective chart review of patients with MMR deficiency on routine immunohistochemistry (IHC) for gastrointestinal malignancies between January 2024 and November 2024 at the Mount Sinai Hospital, a large urban academic medical center. Patients with deficiencies in MLH1, PMS2, MSH2, or MSH6 were identified using electronic medical records. Among patients with MLH1 deficiency, we evaluated the rate of confirmatory testing with MLH1 promoter hypermethylation or BRAF mutation analysis within 6 months. Among all patients with MMR deficiency, we evaluated the rate of genetic counseling referral, genetic counseling visit completion, and germline testing completion within 6 months.

Results: Between January 2024 and November 2024, we identified 40 patients with MMR deficiency on IHC for tumor-based LS screening. Mean age [SD] was 71 [17.6] years, and 22 (55.0%) were female. 21 (52.5%) were non-Hispanic White, 7 (17.5%) were non-Hispanic Asian, 6 (15.0%) were Hispanic/Latino, 4 (10.0%) were non-Hispanic Black, and 2 (5.0%) were Other. 28 of 40 patients (70%) had loss of expression of MLH1, of which 9 (32.1%) completed confirmatory testing with MLH1 hypermethylation or BRAF mutation analysis within 6 months. Among all 40 patients, 10 (25.0%) were referred to genetic counseling and 8 (20.0%) completed genetic counseling follow-up within 6 months. 17 (42.5%) patients completed germline testing within 6 months, of which 10 (58.8%) were negative for LS, 4 (23.5%) were positive for LS, and 3 (17.6%) were positive for a variant of uncertain significance.

Discussion: These preliminary findings revealed gaps in genetic counseling referral and follow-up, confirmatory testing for MLH1 deficiency, and germline testing completion. Possible future interventions could include reflex BRAF or MLH1 hypermethylation testing for MLH1 deficiency, automated notifications or genetic counseling referral orders after abnormal IHC results, or developing a system for genetic counselors to directly contact patients with abnormal IHC testing.

Disclosures:
Matthew Zhao indicated no relevant financial relationships.
Noam Harpaz: AbbVie – Advisory Committee/Board Member, Consultant. Bristol Meyers Squibb – Advisory Committee/Board Member, Consultant. Eli Lilly and Company – Advisory Committee/Board Member, Consultant. PathAI – Advisory Committee/Board Member, Consultant.
Dana Zalkin indicated no relevant financial relationships.

Matthew Yizong. Zhao, MD, Noam Harpaz, , Dana Zalkin, MD. P2619 - Investigating Care Gaps Following Identification of Mismatch Repair Deficiency in Gastrointestinal Cancers, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.