WHAT IS MICROSATELLITE INSTABILITY TESTING?
A test performed on colon, endometrial or other cancer tissue to identify HNPCC syndrome. This syndrome accounts for the most common form of hereditary colorectal cancer, accounting for approximately 5% of cases. It is an autosomal dominant condition that occurs at a relatively young age, usually before age 50 for the first family member diagnosed. HNPCC syndrome, also known as “Lynch Syndrome,” carries a 50%-60% risk of developing colorectal cancer. Once cancer develops, it progresses rapidly—from polyp to invasive cancer within 3 years. Thus, relatives of individuals with confirmed HNPCC mutation should have heightened surveillance for colorectal cancer. Other cancers associated with the HNPCC mutation are small bowel and endometrial cancers as well as cancer of the ureter or renal pelvis.
Testing for HNPCC identifies mutations in any of 5 genes responsible for repairing mismatched DNA in a region called “microsatellites”. Cancer with this type of mutation demonstrates microsatellite instability in the region of the DNA associated with each of the 5 genes.
Bethesda criteria for testing or HNPCC and microsatellite instability include (Umar et al, 2004):
- Colorectal cancer diagnosed in a patient who is less than 50 years of age.
- Presence of synchronous, metachronous colorectal, or other HNPCC-associated tumours, regardless of age.
- Colorectal cancer with the MSI-H histology diagnosed in a person younger than age 60.
- Colorectal cancer diagnosed in one or more first-degree relatives with an HNPCC-related tumour, with one of the cancers being diagnosed in a person under 50 years of age.
Colorectal cancer diagnosed in two or more first- or second-degree relatives with HNPCC-related tumours, regardless of age.