Characterization of LGR5 expression in poorly differentiated colorectal carcinoma with mismatch repair protein deficiency

BackgroundLeucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell and carcinoma stem cell marker. We examined the relationship between mismatch repair (MMR) protein deficiency and LGR5 expression in poorly differentiated (PD) colorectal carcinoma (CRC).MethodsIn 29 cases of PD-CRC, deficiencies in MMR proteins (MLH1, PMS2, MSH2, MSH6) and beta -catenin expression were identified by immunohistochemistry (IHC). LGR5 expression was examined by the RNAscope assay in tissue microarrays.ResultsLGR5 H-scores in MMR-deficient (MMR-D) cases were significantly lower than those in MMR-proficient (MMR-P) cases (P=0.0033). Nuclear beta -catenin IHC scores in MMR-D cases were significantly lower than those in MMR-P cases (P=0.0024). In all cases, there was a positive correlation between LGR5 H-score and nuclear beta -catenin IHC score (r=0.6796, P<0.001). Even in MMR-D and MMR-P cases, there was a positive correlation between LGR5 H-score and nuclear <beta>-catenin IHC score (r=0.7180, P<0.0085 and r=0.6574, P<0.003, respectively). MMR-D CRC cases showed low expression of LGR5, which may be due to low activation of the Wnt/beta -catenin signaling pathway.ConclusionsOur results reveal the relationship between LGR5 expression and MMR protein profiles in PD-CRC. A further study is warranted to confirm these findings.