Background: Tumours with high-frequency microsatellite instability exhibit unique genotype and phenotype features, whereas the difference between low-frequency microsatellite instability and apparently stable tumours is far from being clear.
Aims: To identify distinctive genetic and pathological characteristics of low-frequency microsatellite instability tumours.
Methods: Microsatellite instability status of 57 sporadic colorectal cancers and its correlation with genetic, pathological and clinical features was analysed.
Results: High frequency microsatellite instability and low-frequency microsatellite instability and apparently stable cancers were different in terms of tumour localisation (p=0.015), frequency of APC mutations (p=0.012), occurrence of Crohn's-like/lymphoid reaction (p=0.0353) and morphological evidence of origin from an adenoma (p=0.0338). Specifically, in low-frequency microsatellite instability cancers, APC mutations were very frequent (76.9%, 10/13) and a Crohn's-like/lymphoid reaction was common (38.5%, 5/13). High-frequency microsatellite instability tumours were preferentially located in the right colon and exhibited a higher frequency of loss of heterozygosity at the FHIT locus compared with low-frequency microsatellite instability and apparently stable cases (p=0.0243). Dukes' stage (p=0.0021), tumour localisation (p=0.0410) and pattern of cancer growth (p=0.0374), were the only factors affecting patient survival. However, a borderline improvement was noted in overall survival in high-frequency microsatellite instability and low-frequency microsatellite instability cancer patients (p=0.062).
Conclusions: These results indicate that low-frequency microsatellite instability tumours have different genetics and histological features and suggest that they are a distinct group of colorectal cancers.