Microsatellite instability and the clinicopathological features of sporadic colorectal cancer

Background and aims-In this study, we prospectively examined the clinical s ignificance of the microsatellite instability (MSI) phenotype in sporadic c olorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice. Methods-DNA was extracted from 310 tumours collected from 302 consecutive i ndividuals undergoing curative surgery for sporadic colorectal cancer. Micr osatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expressio n of MLH1, MSH2, and p53. Results-Eleven per cent of tumours showed high level instability (MSI-H), 6 .8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological gra de, have a mucinous phenotype, and to harbour increased numbers of intraepi thelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) rumours showed loss of staining for MLH1 and a further three tumours showe d absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%. Conclusions-We conclude that the MSI-H phenotype constitutes a pathological ly and clinically distinct subtype of sporadic colorectal cancer. Immunohis tochemical staining for MLH1 and MSH2 represents an inexpensive and accurat e means of identifying such tumours.