Apart from the increased proportion of MSI-H tumours found proximally, there may be an additional interplay with anatomical site (see Figure 2); it has been suggested that the relatively uncommon MSI-H tumours within the rectum (where MSH6 defects may be more common than MLH1 and MSH2) may have a different oncogenic profile [49] and may be associated with worse outcome than the more proximal MSI-H tumours and one that is similar in prognosis to that of CIN phenotype tumours [50]. This evidence concerns the gene MSH6 and neoplasm.