Importantly, the incidence of clinically significant tumours (intermediate risk or high risk based on the NICE classification) was 85% (11 of 13) in the MSH2 carriers and 75% (three of four) in the MSH6 carriers compared with none in the two non-carrier control groups, supporting retrospective reports of a more aggressive phenotype in these groups.6, 7, 16, 17 Seven of 13 tumours diagnosed in MSH2 carriers had Gleason 4 (grade group 3) as the dominant pattern, and three tumours were Gleason score 8 or 9 (grade groups 4–5) and so were more likely to behave aggressively with a worse prognosis. This evidence concerns the gene MSH2 and neoplasm.