Simplified identification of Lynch syndrome: a prospective, multicenter study

Abstract

Background: Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed.

Aims: We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers.

Methods: Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing.

Results: Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome.

Conclusion: This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres.