Accuracy of the routine detection of mutation in mismatch repair genes in patients with susceptibility to hereditary upper urinary tract transitional cell carcinoma

Abstract

To establish the clinical benefits of systematic testing for hMSH6 and hMLH1 mutations in the very rare patients with upper urinary tract transitional cell carcinomas (UUT-TCCs), a clinical predisposition for hereditary tumour and no mutation detected in hMSH2 gene. In all, 164 UUT-TCC specimen blocks were screened for microsatellite instability (MSI); 27 (16%) had high MSI levels. Eight patients (30%) had clinical criteria suspicious of hereditary tumour; in three a mutation in hMSH2 was detected. For the other patients, clinical data were collated, and DNA gene sequences analysed to detect mutations in hMLH1 and in hMSH6 genes. Five patients were assessed (mean age at the diagnosis of UUT-TCC 65.2 years, sd 8, range 54-71; two aged < 60 years). Three patients had a personal history of hereditary nonpolyposis colorectal related-cancer (three colorectal). There were only mutations in hMSH2 gene detected, with none in hMSH6 and hMLH1. For the rare patients with UUT-TCC who are suspected of carrying mismatch repair gene mutations if no hMSH2 mutation is found by genetic testing, complementary DNA sequencing for hMLH1 and hMSH6 mutation does not seem to contribute and should not be recommended in daily practice.