Implementing population-based screening for Lynch syndrome.

Abstract

6600 Background: A myriad of molecular markers has been proposed and tested with the promise of improving cancer care. Few have been validated and even fewer have been implemented in daily clinic. The most common hereditary colorectal cancer entity, Lynch Syndrome, can be identified in a subset of colorectal cancer patients by screening molecular markers for mismatch-repair (MMR) deficiency. We wanted to implement this screening in a Danish region, optimize quality, and describe the results. Methods: All colorectal cancer (CRC) patients diagnosed from October 2010 to September 2012 in the Region of Southern Denmark were included. Immunohistochemistry (IHC) was performed for protein expression of the MLH1, PMS2, MSH2, and MSH6 genes followed by MLH1 methylation analysis in cases with loss of pMLH1. Hereafter the indications for genetic counselling were lack of any MMR-protein – and in case missing pMLH1only those with no promoter-methylation of MLH1. Patients were included irrespectively of stage, post-mortem diagnosis, surgery, or other treatment. Accepted reasons for missed data were insufficient or autolyzed tumor material, but not data missing due to death, no surgery, or any logistic problem. Every 3-6 months the national pathology database was checked for missing data and feedback was given to the clinicians to ensure enrolling of all CRC patients. Results: CRC were diagnosed in 2,120 patients in a population of 1,200,000 with informative data for 1,932 patients at the time of analysis. 1,680 had normal protein expression of all four MMR-genes. 209 lacked pMLH1 of which 11 were not methylated. Loss of pMSH2, isolated pMSH6 or pPMS2 was seen in 23, 11, and 9 cases, respectively. Thus, the established screening program was positive in 54 patients. These patients are offered further genetic counselling and testing. Conclusions: Screening for Lynch Syndrome was feasible in a geographically defined area involving several clinical departments. Molecular screening for hereditary MMR-deficiency was positive in 54 of 1932 patients (2.8 %). Implementation of molecular markers in cancer care can be optimized by support from national databases and formalized quality feed back to the clinicians. Clinical trial information: NCT01216930.