Three algorithms are available for Lynch Syndrome screening. All involve the testing of tumor tissue.
MSI: Approximately 90% of colon tumors from individuals with Lynch Syndrome demonstrate microsatellite instability (MSI), whereas only approximately 15% of sporadic colon tumors do. Thus, MSI testing is useful in determining the likelihood of Lynch Syndrome.
IHC: 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 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 because of MSH6 mutations since MSH6-related tumors are sometimes MSS. On the other hand, IHC alone may not detect cases of Lynch Syndrome because of 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.
More detailed information on MSI, IHC, and MSI and IHC testing, along with supplemental materials, is provided in the sections for each algorithm.
Disclosure and follow-up with patients after a screen-positive result can influence whether they participate in genetic counseling and germline testing.
Two centers, Ohio State University and Cleveland Clinic, have seen substantial increases in patient follow-through after changing their protocols. Keys to high patient follow-through include having a genetic counselor track and disclose positive results to patients, performing automatic reflex testing on a subset of screen-positive patients using BRAF or hypermethylation, and holding follow-up appointments to explain results and obtain informed consent for germline testing.
These are challenges other programs have faced when implementing universal tumor screening for Lynch Syndrome and some of the ways that they have overcome these barriers.