Microsatellite instability in colorectal cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Microsatellite instability (MSI) is implicated in hereditary non-polyposis colorectal cancer (HNPCC) and 15% of sporadic colorectal cancers.
• While MSI's basic mechanisms are still under investigation, its clinicopathological consequences are increasingly understood.

Purpose of the Study:

• To review the molecular mechanisms, clinicopathological implications, and prognostic/predictive value of MSI in colorectal cancer.
• To synthesize current understanding of MSI in colorectal cancer, focusing on recent advancements.

Main Methods:

• A Medline search was conducted using keywords related to MSI in colorectal cancer.
• The search focused on molecular mechanisms, clinicopathological aspects, and prognostic/predictive value, prioritizing articles from the last five years.

Main Results:

• Hereditary MSI arises from germline mutations, while sporadic MSI results from epigenetic silencing.
• Commonly altered genes in MSI tumors include TGF-βRII, BAX, β-catenin, p16INK4A, and PTEN; K-ras, APC, and p53 are rarely affected.
• Polymerase chain reaction (PCR) is a superior MSI detection method over immunohistochemistry, though marker selection poses challenges. Bethesda panel aids HNPCC testing, but general screening guidelines are absent.
• MSI tumors typically present in the proximal colon, are large, and have a favorable prognosis, but their response to adjuvant chemotherapy requires further validation. The role of low-frequency MSI remains debated.

Conclusions:

• Stratifying colorectal cancer research by microsatellite status is crucial.
• Further investigation into the molecular mechanisms and clinicopathological consequences of MSI is warranted.