Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability

Abstract

IntroductionColorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important.GoalsOur purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution.Material and methodsThe cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity.ResultsGenerally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.

Ex vivo explant model of adenoma and colorectal cancer to explore mechanisms of action and patient response to cancer prevention therapies

“…Risk factors for adenoma progression to cancer include large adenoma size, villous type histology, and increased levels of dysplasia [ 8 ]. DNA mismatch repair deficiency (dMMR) is observed in 12% of sporadic CRCs [ 9 ], 3% of inherited cancers [ 9 ], and 10% of adenomas [ 10 ]. These tumours have a higher mutational load than microsatellite proficient lesions leading to a robust immune response [ 11 ] which can be potentiated by immunotherapy agents such as Nivolumab or Pembrolizumab [ 12 ].…”