MSI versus MSS sporadic colorectal cancers: Morphology, inflammation, and angiogenesis revisited.

Abstract

495 Background: MSI is a well-documented pathway in the pathogenesis of colorectal cancer. A specific cphenotype has been associated with MSI tumors, as they tend to be more right-sided, have a better prognosis, mostly display a poor histologic differentiation and are marked by extensive inflammation. However, the biological basis and of all these features is still largely unknown. We hypothesize that MSI results in an accumulation of intratumoral mutations. Consequencely, lots of aberrant proteins are formed, probably resulting in a poor histologic differentiation but also evoking a strong immune response that may have the ability to limit tumor expansion (hence explaining a better prognosis) and to stimulate angiogenesis. Methods: To sustain this hypothesis we compared 35 MSI and 35 MSS tumors (matching for TNM staging) with respect to their morphology, inflammation and vessel density. Morphology was analyzed on HE stains. Immunohistochemical stainings for CD 3, CD4, CD8, CD20 and CD68 were performed to document the number of T-lymphocytes, B-lymphocytes and macrophages in relation to tumor location (intraepithelial, intratumoral, peritumoral). CD 31 staining was performed to highlight vessel density in the tumor and assess angiogenesis. Conclusions: (1) In accordance with literature, MSI tumors occured at younger age, with preponderance of the right colon and with a smaller likelihood of metastasis. (2) The most striking observation was the higher number of intra-epithelial T-lymphocytes in MSI tumors (not present in their microsatellite stable counterparts). No difference was found between MSI and MSS tumors in terms of intra/peritumoral B-cells, macrophages, and/or T-cells. (3) Half of the MSI tumors and none of the MSS tumors displayed different histological subtypes/patterns within one tumor. As such, we suggest that in daily routine practice, presence of morphologic tumor heterogeneity should initiate analysis for microsatellite instability. (4) MSI tumors had a statistically much higher (micro)vessel density as compared to their MSS counterparts, hence hinting at a potential application of anti-VEGF therapy in this subgroup of colorectal cancers.