Role of endoscopic biopsies and morphological features in predicting microsatellite instability status in gastric cancer

Abstract

Evaluation of mismatch repair protein (MMR) and microsatellite instability (MSI) status is of pivotal interest for the management of gastric cancer (GC) patients. In this study we aimed to evaluate the accuracy of gastric endoscopic biopsies (EB) in predicting MMR/MSI status and to uncover morphologic features associated with MSI. A multicentric series of 140 GCs in which EB and matched surgical specimen (SS) were available was selected retrospectively. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMRs and by multiplex-polymerase chain reaction (mPCR) for MSI-status. IHC accurately predicted MMR status in EB, with a sensitivity of 100%, a specificity of 94% and high concordance rates between EB and SS (Cohen's kappa=99%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in predicting MSI status (72% vs 100%), while maintaining high specificity (99.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified histopathological features that should prompt the search for MMR/MSI status in GC, despite the morphological heterogeneity of GC cases harboring this molecular phenotype. These features included the presence of mucinous and/or solid components (p=0.034 and p<0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation (p<0.001). Both solid areas and extracellular mucin lakes were discriminating features for the identification of MSI-high cases also in EB (p=0.002 and p=0.045).