Figure 1
From: Economic evaluation of genetic screening for Lynch syndrome in Germany
Overview of screening strategies. Strategy 1 starts with IHC testing, followed by genetic sequencing if results were abnormal. Strategy 2 in addition involves testing for the BRAF V600E mutation as an intermediate step in case the MLH1 protein is absent. If this mutation is found in an MLH1-absent tumor, the cancer is most likely sporadic, and further testing is omitted. Strategy 3 involves sequential IHC and MSI analysis, which must both have a positive result to trigger genetic testing. In contrast to this, Strategy 4 foresees MSI testing in case of a negative IHC test result, and genetic testing is performed if indicated by either method. Strategy 5 starts with MSI testing, followed by both IHC testing and genetic sequencing in case of a positive MSI result. Strategy 6 comprises MSI testing only. Strategy 7 assumes direct sequencing of the MMR genes. All seven baseline strategies may be combined with the Amsterdam II (A) or revised Bethesda (B) criteria. Testing is then offered only to patients who fulfill the clinical criteria. The resulting testing strategies are termed A 1–7 and B 1–7. BRAF, BRAF V 600E mutation testing; DNA, genetic sequencing to identify mutations in the MMR genes; IHC, immunohistochemistry; MSI, microsatellite instability.
