Question

Role of MSI in carcinoma colon.

Hint:

MSI testing is increasingly used to guide treatment decisions, particularly in the context of immunotherapy for colorectal cancer.

Answer 1

Microsatellite instability (MSI) is a condition of genetic hypermutability that occurs when the DNA mismatch repair (MMR) system is defective. In colon carcinoma, MSI plays a crucial role in tumorigenesis and is a marker for prognosis and therapy response.
Step 1: Mechanism of MSI in Colon Carcinoma:
MSI occurs when there are defects in the MMR system, leading to an accumulation of mutations in microsatellites, which are short, repetitive sequences of DNA. This can result in the activation of oncogenes or the inactivation of tumor suppressor genes.
Step 2: Clinical Implications:
MSI is often seen in hereditary nonpolyposis colorectal cancer (HNPCC), and patients with MSI-high tumors tend to have a better prognosis. MSI status is important for selecting patients who may benefit from immune checkpoint inhibitors.
Step 3: Role in Treatment and Prognosis:
MSI-high tumors are more likely to respond to immune checkpoint inhibitors like pembrolizumab, making MSI testing essential in the management of colorectal cancer.