The Cost of Detecting Lynch Syndrome by Microsatellite Instability Testing in Community Practice

Abstract

Purpose: Background: Microsatellite instability (MSI) DNA analysis identifies increased length variations of repetitive sequences in the genome that suggest failure of mismatch repair genes and help identify patients with Lynch syndrome. Aim: To calculate the cost to diagnose one case of Lynch syndrome using automatic MSI testing on colonic adenocarcinomas that fulfill one of the first three revised Bethesda criteria. Methods: From April 2007 through July 2009, MSI testing was performed on patients undergoing colon cancer resection who met the first 3 Bethesda Criteria. 898 colorectal adenocarcinomas were diagnosed and 98 (11%) patients met 1 of the first 3 Bethesda criteria and underwent MSI testing. Costs were calculated by determining the total cost of screening strategy using the real costs of procedures and interventions divided by the number of new cases of Lynch syndrome identified. Results: The median age of the study population was 47.1 years, there were 49 males and 49 females; 83% Caucasian. 67 MSI DNA tests were done on individuals < 50 years of age, 16 had synchronous or metachronous tumors and 43 were less than 60 years of age with high-risk histology. Of the 98 colorectal adenocarcinomas analyzed with MSI testing, 22 had a high level of microsatellite instability (MSI-H) defined as 2 or more of the 5 microsatellite loci being unstable. Of the 22 with MSI-H testing, 15 met with a genetic counselor, 3 were not referred, and 4 refused for personal reasons. Immunohistochemistry was performed on 7 of the MSI-H patient samples. There was a loss of expression of MLH1 and PMS2 in 5 patients, MSH2 and MSH6 in 1 patient, and PMS2 alone in 1 patient. 14 of the MSI-H patients underwent germline genetic testing. Ten of the 14 genetic tests were positive for a mutation: 5 patients with MLH1 mutations, 4 with MSH2 mutations, and 1 with a PMS2 mutation. Twelve of the 22 MSI-H patients evaluated met the Amsterdam criteria which included the 10 patients with confirmed germline genetic mutations, one individual refused to meet with a genetic counselor for personal reasons, and one refused genetic testing for financial reasons. The average cost per case detected was $8492. Conclusion: 1. Selective MSI testing can detect previously unrecognized cases of Lynch syndrome. 2. Although all detected cases met the Amsterdam criteria, many patients became aware of their family history only when MSI testing prompted a careful assessment of family history by the genetic counselor. 3. Downstream reductions in cost and premature mortality in relatives of index cases may justify the cost 4. Measures to enhance adherence with genetic counseling and genetic testing are necessary.