About 5% of colon cancer is due to an inherited predisposition. Of inherited colon cancer Lynch syndrome is the most common type. Lynch syndrome causes 2-3% of colon cancer.
At many institutions screening tests are done on tumor tissue (removed at the time of surgery) to identify those who may be at risk for Lynch syndrome.
- The screening tests are IHC(Immunohistochemistry) and/or MSI(Microsatellite Instability)
- IHC uses special staining to look for the presence of 4 proteins (MLH1, MSH2, MSH6 and PMS2). About 20% of colon cancers are missing one of more of these proteins. If a protein is absent further genetic testing may help determine if an individual is at risk for Lynch syndrome.
- Tumors from individuals with Lynch Syndrome are likely to demonstrate loss of mismatch repair protein expression. The pattern of loss observed can provide information about which gene is not functioning properly. As a result, immunohistochemistry (IHC) testing can be helpful both in providing information about the likelihood of Lynch Syndrome and in directing testing for a germline mutation to a specific gene.
- MSI looks to see if there has been an expansion of the DNA genetic material in the tumor compared to normal DNA. This is called MSI-high. About 15% of the time, the MSI test result is high.
- It is important to know that the majority of the time when these tests are abnormal it is not due to Lynch syndrome.