Microsatellite instability (MSI), the molecular phenotype of colorectal cancers with mismatch repair defects was discovered in the last decade of the previous century. As a field of investigation which successfully joins basic and clinical science, MSI is an example of real translational science, starting from the molecular basis of a disease and extending to the clinical arena. In clinical settings, MSI is a diagnostic biomarker leading to the diagnosis of hereditary nonpolyposis colorectal cancer. However, the clinical implication of MSI testing extends to the role of prognostic marker, due to the better outcome of patients with MSI colorectal cancer. Additionally, MSI identified a general lack of response to neo-adjuvant therapy employing 5-fluorouracil. Like predictive markers of response to chemotherapy, the role of MSI is likely not exhausted, as chemotherapy regimens need to take into account the peculiar biological and clinical behavior of MSI cancers.
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