Are immunohistochemical (IHC)/microsatellite instability (MSI) testing necessary as part of Lynch syndrome work-up in the era of multiplex genetic testing?

425 Background: IHC for mismatch repair proteins and MSI are commonly used to direct genetic testing for Lynch Syndrome. Abnormal results in the setting of a positive family history often lead to genetic testing for Lynch syndrome. The often cumbersome process of completing IHC/MSI requires obtaining stored tissue +/- blood from a family member affected with cancer. Upfront genetic testing is not favoured due to concerns about identifying variants of uncertain significance. We performed a review of Lynch syndrome work-up in Ireland, and propose a model that is the reverse of the current international standard, and may expedite and simplify work up of these families. Methods: Data was ascertained from three cancer genetics services in Dublin and included the following variables: date of birth, date of request and reporting results for IHC, MSI and genetic tests. Time intervals were determined for LS work-up for all patients who had the process initiated in these 3 centres. Results: Probands from 50 families referred for LS work-up were included.The median time from date of IHC request to date of IHC report (total of 50 patients) was 4 weeks (range: 4 days to 36 weeks). The median time between date of IHC request to date of MSI report (n = 32 patients) was 20 weeks (range: 4 to 56 weeks). The median time from date of genetic test request to date of result (n = 9 patients) was 9 weeks (range: 2 to 26 weeks). The median time for completion of all 3 tests in one individual (n=3 patients) was 14 weeks (range: 10 to 60 weeks). Conclusions: The diagnostic pathway for Lynch syndrome is cumbersome and often lengthy. Appropriate upfront multiplex genetic testing would expedite the identification of mismatch repair gene mutation carriers. IHC/MSI testing could be used to characterise variants of uncertain significance.