Underutilization of Genetic Counseling and Germline Testing Following Abnormal Mismatch Repair Immunohistochemistry...

This study aimed to assess referral patterns for genetic counseling among colorectal cancer patients with MLH1, PMS2, MSH2 or MSH6 loss, evaluate the completion rates of germline genetic testing in eligible patients, and identify barriers to genetic evaluation in this population.

We conducted a retrospective chart review of 102 patients with CRC who demonstrated loss of MLH1, PMS2, MSH2, or MSH6 expression on MMR immunohistochemistry between January 2022 and December 2024 across a large healthcare system. In cases with MLH1 loss, reflex tumor testing for BRAF V600E mutation and MLH1 promoter hypermethylation was used to exclude likely sporadic etiologies. Patients with BRAF mutation or MLH1 promoter hypermethylation were excluded, resulting in a final sample of 63 patients eligible for genetic counseling referral. Data collected included demographic characteristics, MMR protein status, site of care (university or community), referral to genetic counseling, completion of germline testing, and documented barriers to referral or follow-through.

Among the 63 eligible patients, the mean age was 69.8 years, and 55.6% were female. The cohort included 60.3% White, 30.2% African American, and 9.5% Asian patients. A total of 36.5% were seen at a university hospital and 63.5% at community hospitals. In adjusted analyses, patient age was the only characteristic significantly associated with referral, with patients aged ≤60 years more likely to be referred than older patients. Despite meeting eligibility, only 38% of patients were referred for genetic counseling. Of those referred, 54.2% completed germline testing, representing 20.6% of the total cohort. The most common barrier was lack of provider referral, affecting 63% of patients.

Despite clear eligibility criteria, fewer than 40% of patients were referred to genetic counseling, and only one in five completed germline testing. The most significant barrier was the lack of provider referral. These findings highlight the need for system-level interventions, including automated referrals, improved communication tools, and navigation support to ensure access to genetic services.