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An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver.

ABSTRACT: The liver is the commonest site of cancer metastasis. In this study, we asked whether the immune tumor microenvironment in liver metastases was governed by the β-catenin activation status of the tumor. To this end, we analyzed CD8 and FoxP3 immunohistochemical expression against β-catenin expression status of the tumor in a cohort of 52 liver samples with metastatic carcinoma. The results showed that colorectal primary constituted the largest proportion of metastatic carcinoma showing β-catenin overexpression. Intra-tumoral CD8 count was lower and FoxP3 count was higher when compared with the non-tumoral liver parenchyma. β-catenin overexpression was associated with a lower CD8 count in the tumor region (p = 0.003). In summary, our findings are in support of an altered immune tumor microenvironment vs. the non-tumor liver tissues in the metastatic site. Suppression of CD8 count was associated with activated Wnt/β-catenin signaling in the metastatic tumor.

SUBMITTER: Au KY

PROVIDER: S-EPMC8262218 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver.

Au Kwan-Yung KY Lo Regina Cheuk-Lam RC

Pathology oncology research : POR 20210604

The liver is the commonest site of cancer metastasis. In this study, we asked whether the immune tumor microenvironment in liver metastases was governed by the β-catenin activation status of the tumor. To this end, we analyzed CD8 and FoxP3 immunohistochemical expression against β-catenin expression status of the tumor in a cohort of 52 liver samples with metastatic carcinoma. The results showed that colorectal primary constituted the largest proportion of metastatic carcinoma showing β-catenin ...[more]

PMID: 34257613

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Project description:BackgroundInflammation is believed to influence human colorectal carcinogenesis and may have an impact on prognosis and survival. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumor-infiltrating immune cells (TIIs) are different in normal colonic tissue vs benign stages (adenomas) and malignant stages (adenocarcinomas) of canine colorectal carcinogenesis, and thus, whether they can be considered as prognostic factors in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n = 18) and adenocarcinoma (n = 13) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized for reasons not involving the gastrointestinal tract served as control tissue (n = 9).ResultsThe tumor samples had significantly lower numbers of CD3+ T-cells in the epithelium compared to controls (adenocarcinoma vs control, Kruskal-Wallis test, p = 0.0004, and adenoma vs control, p = 0.002). Adenomas had a significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Kruskal-Wallis test, p = 0.008). Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. Compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (adenoma vs control Kruskal-Wallis test, p = 0.004, and adenocarcinoma vs control, p = 0.002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinomas and adenomas showed moderate to strong staining of the cell nucleus. The nuclear β-catenin expression (signal strength and distribution) was significantly higher in adenomas compared to adenocarcinomas (Kruskal-Wallis test, p < 0.05).Conclusionsβ-catenin and Ki67 were not useful markers for demonstrating tumor progression from adenomas to adenocarcinomas. The lower presence of CD18 and CD3+ cells in colorectal tumors compared to controls indicates a reduced presence of histiocytes and T-cells, which may have implications for the pathogenesis and progression of colorectal cancer in dogs.

Project description:BackgroundDeregulation of Wnt/β-catenin signaling is a hallmark of the majority of sporadic forms of colorectal cancer and results in increased stability of the protein β-catenin. β-catenin is then shuttled into the nucleus where it activates the transcription of its target genes, including the proto-oncogenes MYC and CCND1 as well as the genes encoding the basic helix-loop-helix (bHLH) proteins ASCL2 and ITF-2B. To identify genes commonly regulated by β-catenin in colorectal cancer cell lines, we analyzed β-catenin target gene expression in two non-isogenic cell lines, DLD1 and SW480, using DNA microarrays and compared these genes to β-catenin target genes published in the PubMed database and DNA microarray data presented in the Gene Expression Omnibus (GEO) database.ResultsTreatment of DLD1 and SW480 cells with β-catenin siRNA resulted in differential expression of 1501 and 2389 genes, respectively. 335 of these genes were regulated in the same direction in both cell lines. Comparison of these data with published β-catenin target genes for the colon carcinoma cell line LS174T revealed 193 genes that are regulated similarly in all three cell lines. The overlapping gene set includes confirmed β-catenin target genes like AXIN2, MYC, and ASCL2. We also identified 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that are regulated similarly in DLD1 and SW480 cells and one pathway - the steroid biosynthesis pathway - was regulated in all three cell lines.ConclusionsBased on the large number of potential β-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T cells as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study Wnt/β-catenin signaling and associated colorectal carcinogenesis. Furthermore, the confirmed and the newly identified potential β-catenin target genes are useful starting points for further studies.

Dataset Information

An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver.

Publications

An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver.

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