The analysis of microsatellite instability in extracolonic gastrointestinal malignancy

Microsatellite instability (MSI) is a genetic feature of sporadic and familial cancers of multiple sites and is related to defective mismatch repair (MMR) protein function. Lynch syndrome (LS) is a familial form of MMR deficiency that may present with a spectrum of MSI positive cancers including gastrointestinal (GI) malignancies. The incidence of high level MSI (MSI-H) in colorectal carcinoma is well defined in both familial and sporadic cases and these tumours portend a better overall prognosis in colorectal carcinoma (CRC). There are certain morphological features that suggest MSI-H CRC and international guidelines have been established for the evaluation of MSI in CRC. The prevalence and morphological features of extracolonic GI MSI-H tumours are less well documented. Furthermore, it is unclear whether the guidelines for the assessment of MSI in CRC are appropriate for application to extracolonic GI malignancies. This review aims to summarise the recent literature on MSI in extracolonic LS-related GI tract malignancies with special attention to the assessment of the MMR system by evaluation of specific microsatellite markers and/or immunohistochemical evaluation of MMR protein expression. The reported prevalence of sporadic and LS-related MSI-H tumours along with their associated unique morphological patterns and related prognostic or therapeutic implications will be discussed.