Background: Current guidelines recommend a step-wise screening algorithm for all colorectal carcinomas (CRC) to identify patients with Lynch syndrome (LS).
Aim: To describe the frequencies of mismatch repair deficiency (dMMR), BRAFV600E mutations and MLH1 methylation in resected CRC, and evaluate the impact of universal screening on LS detection.
Methods: Retrospectively, 1171 consecutive cases of resected CRC were identified between 2010 and 2017 from a large multi-centre pathology service. Testing for dMMR by immunohistochemistry (IHC) was initiated by the reporting pathologist from 2010, until universal testing was introduced in 2015. Patients with dMMR were referred to the Family Cancer Clinic (FCC) for consideration of germline mutation analysis.
Results: IHC was performed on 680 tumours, with abnormal expression in 124 (18%). Referral to FCC was made for 44 of the 88 patients with abnormal IHC (excluding those with BRAFV600E mutations). Of the 29 who attended, 16 underwent germline genetic testing, and LS was diagnosed in 7 with a germline mutation. After implementation of universal testing, there was a greater incidence of dMMR (17% vs 10%, P = 0.02), rate of BRAFV600E testing (79% vs 25%, P < 0.0001), and referral to FCC (61% vs 33%, P < 0.0001), but no difference in FCC attendance rate (65% vs 67%, P = 0.59) or new LS diagnoses (1.6% vs 0%, P = 0.06).
Conclusion: Universal IHC testing may increase the detection of LS, and should be implemented where possible. However, the full benefit was limited by low referral to and uptake of genetic testing, and further strategies are needed to overcome these barriers.
Keywords: Lynch syndrome; genetic counselling; immunohistochemistry; mismatch repair; universal screening.
© 2019 Royal Australasian College of Physicians.