The 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.

3. Colorectal cancer with the MSI-H^¶-like histology^Δ diagnosed in a patient who is less than 60 years of age^◊.

4. Colorectal cancer diagnosed in a patient with 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 a patient with two or more first- or second-degree relatives with HNPCC-related tumors, regardless of age.

HNPCC: hereditary nonpolyposis colorectal cancer; MSI-H: microsatellite instability-high.
* HNPCC-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, and brain (usually glioblastoma as seen in Turcot syndrome) tumors, sebaceous gland adenomas and keratocanthomas in Muir-Torre syndrome, and carcinoma of the small bowel.
¶ MSI-H in tumors refers to changes in two or more of the five National Cancer Institute-recommended panels of microsatellite markers.
Δ Presence of tumor infiltrating lymphocytes. Crohn's-like lymphocytic reaction, mucinous/signet-ring differentiation, or medullary growth pattern.
◊ There was no consensus among the Workshop participants on whether to include the age criteria in guideline 3 above; participants voted to keep less than 60 years of age in the guidelines.

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