Using Immunohistochemistry to Expand the Spectrum of Lynch Syndrome-Related Tumors

Abstract

The most common genetic and molecular process leading to sporadic colorectal cancer is chromosomal instability. By contrast, mismatch repair deficiency, which results in high levels of microsatellite instability or lack of mismatch repair (MMR) protein expression on immunohistochemistry (IHC), is the predominant cancer pathway in patients with Lynch syndrome (LS). Importantly, patients with LS may still develop sporadic tumors through chromosomal instability. Testing tumors with IHC staining helps expand the spectrum of LS-related tumors. In this series, we describe 4 cancers in patients with LS that are not typical of the syndrome. Lack of MMR protein expression on IHC staining confirmed that 2 cancers are related to LS, expanding the spectrum of LS-related tumors, and the presence of MMR protein expression on IHC in the other 2 cases confirmed that they were sporadic and not related to mismatch repair deficiency and, thus, not related to LS.