Lower GI 01

Background: Tumours from patients developing multiple colorectal cancers (CRC) demonstrate a high incidence of microsatellite instability (MSI). This does not predict the development of multiple disease, since 15 per cent of sporadic CRC also demonstrate MSI. This study aims to investigate the relationship between MSI and cancer location in predicting the risk of a second cancer. Methods: The MSI status of 100 CRC from 49 patients who developed multiple CRC (26 metachronous and 23 synchronous) were compared with 102 patients with a single CRC. Microsatellite analysis by PCR and SSCP was performed on extracted DNA at the loci Bat25, Bat26, Bat40, D2S123, D5S346 and D17S250. Cancers were classified as high-level MSI (MSI-H) when >30 per cent of loci were unstable, low (MSI-L) when <30 per cent were unstable, or stable (MSS) if MSI was absent. Results: The median age of those with multiple cancers was 70 years (range: 33–100) and single cancer was 72 years (range: 35–84). MSI-H was demonstrated in 11 per cent of single and 51 per cent of multiple cancers (P < 0.001). The incidence of MSI-H is shown below. There was no difference in the incidence of proximal MSI-H cancers, but MSI-H cancers in the distal colon occurred 14–18 times more frequently in the multiple group (P < 0.001). Conclusion: MSI-H cancers identified distal to the splenic flexure should alert clinicians to the possible existence of a synchronous lesion or subsequent development of a metachronous cancer.