Explaining an Atypical Immunohistochemical Pattern Using Paired Tumor/Germline Testing for Lynch syndrome
Paired tumor/germline testing fully explained atypical IHC results (abnormal staining of MLH1 and/or PMS2 in addition to abnormal staining of MSH6) in 10% of cases and partially explained the IHC pattern in an additional 33% of cases, while germline testing alone would not have fully explained any cases, showing that paired testing can improve clinical utility compared to germline testing alone in cases with atypical IHC results.
Our data supports previous research showing that somatic MSH6 coding microsatellite mutations can contribute to abnormal MSH6 IHC staining in cases that also demonstrate abnormal MLH1 and/or PMS2 staining, and paired testing results were concordant with the atypical IHC pattern in 37% of cases, but did not fully explain abnormal MSH6 staining due to the presence of only a single somatic CM mutation.
Our data confirms that this atypical IHC pattern can be fully explained by paired tumor/germline testing in 10% of cases, while other cases may be partially or completely unexplained due to possibly erroneous IHC results, potentially undetected germline or somatic alterations, or other causes.
Speakers: Kelly Fulk; Carla Mason; Monalyn Umali Salvador; Holly LaDuca; Swati Shah