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Revised Bethesda Guidelines for testing colorectal tumors for microsatellite instability (MSI)

Tumors from individuals should be tested for MSI in the following situations:

1. Colorectal cancer diagnosed in a patient who is less than 50 years of age.

2. Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumors*, regardless of age.
*Colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain (usually glioblastoma as seen in Turcot syndrome) tumors, sebaceous gland adenomas & keratoacanthomas in Muir-Torre syndrome, and carcinoma of the small bowel

3. Colorectal cancer with MSI-H histology* diagnosed in a patient who is less than 60 years of age.
*Presence of tumor-infiltrating lymphocytes, Crohn’s-like lymphocytic eaction, mucinous/signet ring differentiation, or medullary growth pattern.

4. Colorectal cancer diagnosed in one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under age 50 years.

5. Colorectal cancer diagnosed in two or more first-degree relative with HNOCC-related tumors, regardless of age.
Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability

Download the NIH PDF file

Hereditary non-polyposis colorectal cancer (HNPCC) is usually caused by a mutation in a mismatch repair (MMR) gene. To date, there are four mismatch repair genes linked to HNPCC — MLH1, MSH2, MSH6, and PMS2. Mutations in MLH1 and MSH2 account for about 90% of all HNPCC mutations. Another gene, called EPCAM also interferes with mismatch repair by interaction with the MSH2 gene. It is responsible for a small number of HNPCC cases.