Abstract
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 β-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 β-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 β-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 β-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/β-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.
Highlights
Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell and carcinoma stem cell marker
We investigated the relationship between LGR5 and β-catenin expression related to LGR5 regulation, and that between CD8positive tumor-infiltrating lymphocytes (CD8 + Tumor-infiltrating lymphocytes (TILs)) and LGR5 expression in immune responses
Correlations between clinicopathological factors and mismatch repair (MMR) protein expression We first evaluated the expression of MMR proteins (MLH1, PMS2, MSH2, and MSH6) in 29 poorly differentiated (PD)-CRC cases
Summary
Leucine-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). Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a promising intestinal stem cell marker [1]. LGR5 is a candidate marker for colorectal cancer (CRC) stem cells [2] and may be closely involved in the progression and prognosis of CRC [3]. 70–80% of CRCs have APC inactivation, which has a major role in adenoma formation, and subsequent multistage mutations such as KRAS and TP53 mutations that cause carcinogenesis [8]. Mismatch repair (MMR) proteins such as MLH1, MSH2, MSH6, and PMS2 are inactivated, and gene
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