Tumor molecular signatures: bridging the bench and the operating room

Contemporary diagnostic and therapeutic strategies for many solid tumors rely on understanding the Mismatch Repair (MMR) system, a fundamental DNA repair mechanism responsible for correcting errors introduced during DNA replication. Pathology reports written for tumors excised in surgery, often indicate the expression status of MMR proteins. This is of significant clinical value, as loss of MMR protein expression is associated with the accumulation of DNA replication errors.

The MMR system recognizes and replaces mismatched nucleotides, particularly in microsatellite regions. These are short, repetitive non-coding DNA sequences prone to replication errors. When MMR proteins are inactivated by genetic or epigenetic alterations, MMR deficiency (dMMR) occurs, preventing repair and leading to microsatellite instability (MSI). MSI is a hallmark of Lynch syndrome, which is commonly associated with colorectal cancer (CRC) and endometrial cancer.

This work highlights the clinical utility of MMR protein and MSI status as molecular signatures and discusses diagnostic, prognostic, and therapeutic implications. Understanding these molecular changes supports clinicians in making informed therapeutic decisions and may improve patient outcomes by providing personalized treatments to fit individual tumor profiles.