Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer

Background: Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behaviour. This study analyses the associa tion between extensive MSI (MSI-H), clinicopathological features and surviv al in an unselected group of patients with sporadic Australian Clinico-Path ological Stage (ACPS) C (tumour node metastasis stage III) colorectal cance r. Methods: Some 255 patients who underwent resection for sporadic ACPS C colo rectal cancer between 1986 and 1992 were studied. No patient had received c hemotherapy. Minimum follow-up for all patients was 5 years. Archival norma l and tumour DNA was extracted and amplified by polymerase chain reaction u sing a radioactive labelling technique. MSI-H was defined as instability in 40 per cent or more of seven markers. Results: Twenty-one patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right side d (P < 0.00001), larger (P = 0.002) and more likely to be high grade (P = 0 .049). After adjustment for age, sex and other pathological variables, pati ents whose cancers exhibited MSI-H had improved survival (P = 0.015). Conclusion: Recognition of MSI-H in sporadic ACPS C tumours identifies a su bset of cancers with improved prognosis. Such stratification should be cons idered in trials of adjuvant therapy and may be relevant to therapeutic dec ision making.