Effect of genetic counseling on detection of Lynch syndrome (LS) in colorectal cancer (CRC) patients (pts).

Abstract

419 Background: LS, characterized by germline mutations in MLH1, MSH2, MSH6, or PMS2, leads to defective DNA mismatch repair (dMMR) and causes 2%-3% of CRC cases. Ohio State University (OSU) began immunohistochemistry (IHC) screening on all CRC cases in 2006. In 2006 results were reported in pathology reports without further follow-up. From 2007 to 2010 genetic clinic (GC) counselors contacted pts and recommended further testing. Since 2011, GC counselors met pts at a follow-up appointment. This retrospective study aims to assess if type of follow-up after abnormal IHC, affects rate of conclusive testing. Methods: All CRC pts diagnosed at OSU from 03/06-06/12 had MMR testing per IHC. All pts’ charts were reviewed. Conclusive testing, following the initial MMR IHC, includes either MLH1-hypermethylation testing and/or gene sequencing to identify LS from non-LS pts. Chi-square test was used for categorical parameters and t-test for continuous variables to compare differences between pts with conclusive test vs those without. Results: One-hundred and twenty two tumors of 777 (15.7%) tested had dMMR by IHC. The GC follow-up of abnormal results significantly affected the rate of conclusive testing. The rate of conclusive testing went from 14.3% in 2006 to 38.4% in 2007-2010 and after 2011, 90.5% of the pts had conclusive testing done. Among 51 pts undergoing full testing, 13 pts were diagnosed with LS, 29 pts had MLH1-hypermethylated tumors, and 9 pts were not found to have any mutations on gene sequencing. Conclusions: Conclusive testing rates after abnormal universal screening with IHC improved significantly with GC involvement and was most effective when GC counselors met with the pts during their appointment. [Table: see text]