Current guidelines recommend a step-wise screening algorithm for all colorectal carcinomas (CRC), to identify patients with Lynch Syndrome (LS). We investigated the impact of pathologist-initiated and universal screening with immunohistochemistry (IHC) on screening rates, LS diagnosis, and rates of referral to the genetic counselling service.
Retrospectively, 1171 consecutive cases of resected CRC were identified between 2010-2017 from the database of a large multi-centre pathology service. Testing for mismatch repair deficiency (dMMR) by 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.
IHC for dMMR was performed on 680 (58%) tumours. The rate of testing increased from 19% in 2011 to 98% in 2017. Abnormal IHC expression was found in 124 (18%). To exclude sporadic cases, BRAFV600E mutation testing was performed on 48/105 with loss of PMS2 expression, and a mutation was identified 36 cases. Referral to the FCC was made for only 50% (44/88) of patients with abnormal IHC and no BRAFV600E mutation. Of the 29 who attended an appointment, 16 underwent germline genetic testing, from which 7 were diagnosed with LS. After implementation of universal testing, there was a greater incidence of dMMR, rate of BRAFV600E testing, and referral to FCC, but no difference in FCC attendance rate or new LS diagnoses (Table).Table: 118P
Before and after implementation of universal screening
|n = 320||n = 321|
|dMMR incidence||10% (33/320)||17% (54/321)||0.02|
|BRAF testing in PMS2 deficient||25% (8/32)||79% (34/43)||<0.01|
|Referral to FCC*||33% (9/27)||61% (17/28)||<0.01|
|Attendance at FCC||67%||65%||0.59|
BRAFV600E mutant excluded
Universal screening using IHC for MMR has the potential to increase identification of patients at risk of Lynch Syndrome, and should be implemented where possible. However, the full benefit of universal screening was limited by the low uptake of genetic testing, and further strategies are needed to overcome these barriers.
Clinical trial identification
Legal entity responsible for the study
Austin Health Human Research Ethics Committee.
Has not received any funding.
All authors have declared no conflicts of interest.