Do Microsatellite Instability Profiles Really Differ Between Colorectal and Endometrial Tumors?

Microsatellite instability (MSI) occurs in more than 90% of the tumors of Lynch syndrome patients, and in 15-25% of sporadic colorectal (CRC) and endometrial carcinomas (EC). Previous studies comparing EC and CRC using BAT markers showed that the frequency of unstable markers is lower in EC, and that the size of the mutations is smaller in EC. In the present study, we analyzed the type (insertions/deletions), size, and frequency of mutations occurring at three BAT and three dinucleotide markers in CRC and EC, to elucidate whether it is possible to establish different MSI profiles in carcinomas of different tissue origin. We show that mononucleotide markers nearly always become shorter whereas dinucleotide markers can become shorter or longer, in both CRC and EC. We therefore conclude that the type of mutation is a marker-dependent feature rather than tissue-dependent. However, we observed that the size of the deletions/insertions differs between CRC and EC, with EC having shorter alterations. The frequency of mono- and dinucleotide instability found in both tissues is comparable, with mononucleotide and dinucleotide markers being affected at similar rates. We conclude that it is not possible to define clearly different MSI profiles that could distinguish MSI-high in CRC and EC. We propose that the differences observed might indicate different durations of tumor development and/or differences in tissue turnover between colorectal and endometrial epithelium, rather than reflecting truly different MSI profiles. We therefore suggest that the same MSI tests can be used for both tumor types. (C) 2009 Wiley-Liss, Inc.