Table 2

 Estimated outcomes from HNPCC testing with and without BRAF-V600E analysis*

IHC, immunohistochemistry.
*Calculations were carried out according to previously published data.14,30 The number of cases showing MSI-H when using unselected cohorts of tumours is calculated assuming that 12% of cases will be positive, whereas the total number of HNPCC cases is estimated considering that 2.7% of total tumours will be HNPCC as reported previously1; †Assuming that half of the newly diagnosed HNPCC cases show altered MSH2 IHC; ‡The number of sporadic MSI-H cases has been estimated from the total number of MSI-H cases to be tested for MMR defects and the number of HNPCC cases showing MLH1 or MSH2 mutations, assuming that they represent 50% of the total HNPCC cases; §The total number of BRAF positive cases has been estimated from our own results, assuming that 40% of the obtained sporadic MSI-H cases will be positive; ¶These cases will not have to be analysed for MSH2.
Using the Bethesda guidelines
Newly diagnosed cases per year: 129 40014,30
Cases selected for MSI testing: 20 83314
Positive cases showing MSI-H for MMR tests: 298014
Newly diagnosed HNPCC cases showing MLH1 or MSH2 alterations: 86014
Estimated newly diagnosed HNPCC cases showing altered IHC of MSH2: 430†
Positive cases showing MSI-H for MMR tests after MSH2 IHC: 2550 (2980–430)
Number of sporadic MSI-H cases: 1260‡
Estimated number of BRAF positive cases: 504§
Reduction rate in MMR testing by BRAF analysis: 17% (504/2980×100)
Reduction rate in MMR testing by BRAF after MSH2 IHC: 20% (504/2550×100)¶
Using unselected cohorts of colorectal tumours
Newly diagnosed cases per year: 129 40014,30
Positive cases showing MSI-H for MMR tests: 15 528
Total newly diagnosed HNPCC cases: 3483
HNPCC cases showing MLH1 or MSH2 alterations: 1747
Estimated newly diagnosed HNPCC cases showing altered IHC of MSH2: 873†
Positive cases showing MSI-H for MMR tests after MSH2 IHC: 14 655 (15 528–873)
Number of sporadic MSI-H cases: 12 034‡
Estimated number of BRAF positive cases: 4813§
Reduction rate in MMR testing by BRAF analysis: 31% (4813/15 528×100)
Reduction rate in MMR testing by BRAF after MSH2 IHC: 33% (4813/14 655×100)¶