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BAT‐26 identifies sporadic colorectal cancers with mutator phenotype: a correlative study with clinico‐pathological features and mutations in mismatch repair genes

Microsatellite instability (MSI) is present in most colorectal cancers (CRC) associated with hereditary nonpolyposis colorectal cancer (HNPCC). MSI testing in so‐called sporadic forms of CRC may become a useful tool in identifying new HNPCC kindred. The aim of this study was to analyse the utility of BAT‐26 as a marker to identify CRCs with MSI and to investigate whether sporadic CRCs with MSI have a phenotypic expression similar to HNPCC cases. MSI was detected using two methods, an association of 7 poly(CA) repeats and a poly(A) repeat alone, BAT‐26, in a series of 62 patients with apparently sporadic forms of CRC. Germ‐line and somatic mutations in the hMSH2, hMLH1, and hMSH6 genes were analysed in patients with MSI+ tumours. Patients with MSI+ at poly(CA) loci and at BAT‐26 were younger (p = 0·024 and p = 0·002), had tumours more frequently right sided (p = 0·017 and p = 0·0001) and more often mucinous (p = 0·037 and p = 0·005, respectively) than patients with MSI negative tumours. Mutation analysis allowed the identification of two patients carrying germ‐line mutations in the hMLH1 gene (both were BAT‐26+) and two other patients who had somatic mutation in the hMSH2 and in hMLH1 genes. In conclusion, the detection of MSI using poly(CA) repeats or BAT‐26 alone allowed the identification of a subset of patients with clinico‐pathological characteristics similar to those associated to HNPCC. BAT‐26 has the advantage of being a simple and less expensive method that might be used as a screening procedure before mutation analysis. Copyright © 1999 John Wiley & Sons, Ltd.