Implementation

There are multiple Lynch syndrome screening algorithms to choose from.  These are briefly described below and detailed in their respective sections.

MSI: Microsatellite instability (MSI) testing can be performed on tumor tissue to gain more information about the likelihood of Lynch syndrome. Approximately 90% of colon tumors from individuals with Lynch syndrome demonstrate microsatellite instability (MSI), whereas only approximately 15% of sporadic colon tumors do.

IHC: Immunohistochemical (IHC) testing can be performed on tumor tissue to analyze mismatch repair protein function. 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, IHC 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 and IHC: When used alone, MSI and IHC may miss some cases of Lynch syndrome. For example, MSI alone may not detect cases of Lynch syndrome due to MSH6 mutations since MSH6-related tumors are sometimes MSS. On the other hand, IHC alone may not detect cases of Lynch syndrome due to mutations that result in full length, but dysfunctional protein. There is no consensus on whether MSI, IHC, or both is the ideal screening tool for Lynch syndrome. Some centers start with MSI testing and then perform IHC on tumors that demonstrate microsatellite instability to help direct genetic testing. Others use IHC as the sole screening tool. Some centers perform both tests simultaneously to provide as much information as possible.