Microsatellite instability and allelic imbalance in primary and secondary colorectal cancer

Background: Several studies of colorectal cancer have shown an association between the number and type of genomic defects and the stage of disease. A subset of colorectal rumours are due to inactivation of DNA mismatch repair genes and these rumours exhibit microsatellite instability. The aim of the present study was to compare and contrast the genomic defects present in b oth the primary and metastatic stages of the disease using microsatellite p robes. Methods: Modifications of the allelic profiles of 25 microsatellite regions were studied in a total of 85 colorectal rumours using fluorescent polymer ase chain reaction (PCR) technology and subsequent direct analysis on an au tomatic sequencer. This approach was used because it allows the study of mi crosatellite instability and allelic imbalance. Stepwise logistic regressio n analysis was used to develop a model to predict whether the tumour was pr imary or secondary from the percentage of allelic imbalance. Subsequently, a group of 17 patients with primary colorectal tumours was analysed prospec tively to test the proposed model. Results: Six of 39 primary tumours showed microsatellite instability compar ed to 0 of 29 liver metastases (P = 0.03). Primary tumours showed significa ntly less allelic imbalance than liver metastases (P < 0.001). Three probes (d18s53, d9s158 and d10s191) were selected for use in a model to classify a tumour as primary or secondary on the basis of the degree of allelic imba lance. When tested prospectively this model had a specificity of 82%. Conclusions: The present study demonstrates the potential importance of usi ng microsatellite probes both as a diagnostic tool and as a research techni que to investigate the mechanisms of tumour progression. An important clini cal finding is that none of the colorectal liver metastases showed microsat ellite instability (0 of 29). This analysis also confirmed other work that has shown a direct relationship between the degree of allelic imbalance and the stage of disease.