No Evidence of Microsatellite Instability in Head and Neck Squamous Cell Carcinoma of Non-Smokers and Non-Drinkers

Introduction: While the prevalence of microsatellite instability (MSI) is low in the whole head and neck squamous cell carcinoma (HNSCC) population, it has been suggested to be more prominent in tumors of non-smokers. Therefore, the goal of this study was to determine the presence of MSI in a cohort of well-defined HNSCC of non-smokers and non-drinkers (NSND). Methods: Clinical characteristics and tumor tissue of 119 NSND with HNSCC were retrospectively collected and analyzed for MLH1, PMS2, MSH2, and MSH6 protein expression on tissue microarrays (TMA). In case of negative staining for one of these mismatch repair proteins in the TMA cores, immunohistochemistry (IHC) was repeated on a whole slide section and additional molecular analyses were performed using polymerase chain reaction (PCR) and quantitative PCR (qPCR). Results: Two cases showed dubious loss of MSH2 expression, one of these with concurrent dubious loss of MSH6 on the TMA. However, MSH2 and MSH6 expression was retained on whole slide sections and PCR and qPCR analyses did not show any mutations, compatible with a microsatellite stable result. Conclusion: This study shows no single case with MSI in the NSND subgroup of HNSCC. Although a deficient DNA mismatch repair system is a predictive biomarker for response to immune checkpoint inhibitors, we found no evidence to support routine analysis of MSI in HNSCC, also not in the subgroup of NSND.