Microsatellite unstable colorectal cancer

The paper by Shitoh et al on the pathogenesis of non-familial colorectal carcinomas with high microsatellite instability (MSI) indicates little clinicopathological distinction from microsatellite stable cancers and a similar distribution of mutation in the adenomatous polyposis coli (APC) and TP53 genes, and loss of heterozygosity (LOH) at 17p.¹ The authors claim that their data fit with some earlier studies, but several of the pioneering studies do not distinguish clearly between MSI low (MSI-L) and MSI high (MSI-H) cancers. Their findings are very different from multiple studies that adequately distinguish between sporadic MSI-H and MSI-L cancers.

By way of explanation, the authors suggest that other studies may include hereditary non-polyposis colorectal carcinoma (HNPCC) cases. It is more likely that their own series includes HNPCC cases, because a lack of a family history does not exclude this diagnosis. Given that somatic mutations of hMSH2 and hMLH1 are described in six of their MSI-H cases, these could be examples of HNPCC because methylation of the promoter region of hMLH1 is regarded as the usual pathogenetic basis for non-familial examples of MSI-H colorectal cancer. Again, the failure to identify a germline mutation in these …