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Gryfe R, Kim H, Hsieh E, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000;342:69-77.

- Among patients with colon cancer at an early age (<50 years), 17% had a high frequency of microsatellite instability, not different that what is found in sporadic colon cancers in the general population (>50 years), but much less than in HNPCC syndrome.

- The presence of high frequency microsatellite instability correlated with a better prognosis, and is an independent variable predicting a favorable outcome and reduced likelihood of metastasis.

- Regardless of depth of tumor invasion in the colonic wall, cancers with high-frequency microsatellite instability had a decreased likelihood of metastasis to regional lymph nodes.

- Microsatellite instability refers to increased rates of mutation within the genes (intragenic) characterized by instability of short, frequently repeated DNA sequences.

- These sequences are known as microsatellites, if they change frequently as a result of mutations, then it is called microsatellite instability.

- Microsatellite instability occurs as a result of defective mismatch-repair genes (MSH2 and MLH1). When these mismatch-repair genes are defective, errors in DNA copying are not corrected and the microsatellite sequences are incorrectly copied.

- In contrast, other types of mutations leading to colon cancer are caused by chromosomal instability, that is, there is allelic loss or chromosomal changes such as translocations. Examples include mutations of the APC and p53 genes, where an allele is missing.

- High-frequency microsatellite instability is prognostic of improved survival regardless of pathological stage of the tumor at diagnosis

- Paradoxically, though, tumors with high frequency microsatellite instability usually have features at diagnosis associated with poor prognosis – such as poorly differentiated, or advanced stage. Why the prognosis is better is not understood.

- Microsatellite instability is found in over 80% of patients with HNPCC syndrome, but only 15% of sporadic colon cancers

Patients with high-frequency microsatellite instability detected in their tumors have better prognosis, and probably better survival than those without microsatellite instability, regardless of staging at diagnosis.