Universal Immunohistochemistry Screening for Lynch Syndrome: Real World Lessons from an Academic Institutional Experience

Background and Aims: Lynch Syndrome (LS) is the most common inherited form of Colorectal Cancer (CRC). While current guidelines recommend Universal Molecular Screening (US) of CRCs, the effects of this in clinical practice remains unknown. Methods: Data on adult patients with surgical CRC resection between January 1, 2010 and December 31, 2014 were obtained. Previously diagnosed hereditary cancers, secondary colonic cancers and inflammatory bowel disease associated CRC were excluded. Results: 455 patients were included with mean age 62 years; 74.7% (n=340) underwent US with Immunohistochemistry (IHC). Distal left sided CRCs were less likely to undergo IHC (22.6%, p<0.001) when compared to all other locations. Among those tested with IHC, 17.9% (n=61) had MMR loss; rates of prior personal or family history of uterine or colon cancer were similar regardless of MMR status. 47 (13.8%) patients had IHC consistent with LS of which less than half (47%) were referred for GC. Patients <50 years of age were more likely to receive GC (OR 4.30, 95% CI 2.17-8.52, p<0.001), even in the presence of negative IHC screens (OR 13.23, 95% CI 4.43-39.55, p<0.001). Confirmatory BRAF mutation testing for MLH1/PMS2 loss greatly improved accuracy of identifying LS. Conclusions: A consistent approach to US of CRCs is imperative given that patients with loss of MMR were similar clinically to those with preserved MMR. Distal left sided CRCs should undergo adequate pre-treatment biopsy sampling to allow for US given the barriers to IHC in this location following radiation treatment and resection.