Lights and shadows of microsatellite status characterization in gastrointestinal cancers in the era of cancer precision therapy

: The introduction of immunotherapy has dramatically changed the paradigm of solid tumor treatment with the creation of novel therapeutic opportunities even for tumors that currently lack valid therapeutic options in the advanced or metastatic setting. Initially, the role of deficient mismatch repair status (dMMR)/microsatellite instability (MSI) as a predictive biomarker was confined to colorectal cancer. In 2017, MSI/dMMR became the first true agnostic biomarker to stratify patient response to immune checkpoint inhibitors. MSI/dMMR evaluation is a crucial point in diagnostic-therapeutic decision-making for most gastrointestinal cancer patients and the pathologist must be responsible for the delivery of reliable reporting in this setting. The aim of this review is to summarize the current methods available in routine diagnostics for the evaluation of MSI/dMMR status, their limitations, and potential pitfalls that can be encountered. The authors also give an overview of the role of MSI/dMMR as a prognostic and predictive biomarker in gastrointestinal cancers, with a focus on non-colorectal malignancies.