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Immunohistochemical analysis of beta-catenin, E-cadherin and p53 in canine gastrointestinal epithelial tumors.

ABSTRACT: Wnt/beta-catenin signaling, E-cadherin and p53 reportedly play important roles in the development and/or progression of human gastrointestinal cancer. The present study evaluated the roles of beta-catenin, E-cadherin and p53 in canine gastrointestinal tumors. Endoscopic biopsy or surgically resected samples, a total of 131, including 38 gastric, 13 small intestinal and 80 large intestinal tumors, were obtained from 95 dogs. Those specimens were examined pathologically. Immunohistochemically, nuclear beta-catenin expression was found in 88% (42/48) of polypoid type adenocarcinomas. Most cases of non-polypoid type adenocarcinomas lacked nuclear expression of beta-catenin with the exception of one case (6%, 1/17). Nuclear beta-catenin expression was not observed in signet ring cell carcinomas (0/15), mucinous adenocarcinomas (0/7) and undifferentiated carcinomas (0/4). The findings indicate that nuclear translocation of beta-catenin is closely related to the development of polypoid type adenocarcinomas but not that of non-polypoid type malignant tumors. The immunoreactivity of E-cadherin for tumor cells tended to decline overall in most of cases including benign tumors. Significant immunoreactivity for p53 was not found in 61% of tumors examined (80/131), including malignant tumors (63%, 57/91), while intense p53-immunoreactivity was rarely found in a few cases of malignant tumors (8%, 7/91). We could not conclude clearly significant correlations between histopathological tumor types and immunohistochemical results of E-cadherin or p53. This paper indicates the importance of the nuclear translocation of beta-catenin for the tumorigenesis of canine intestinal polypoid type adenocarcinomas, especially in the colorectum.

SUBMITTER: Saito T

PROVIDER: S-EPMC7538321 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Immunohistochemical analysis of beta-catenin, E-cadherin and p53 in canine gastrointestinal epithelial tumors.

Saito Tsubasa T Chambers James K JK Nakashima Ko K Nibe Kazumi K Ohno Koichi K Tsujimoto Hajime H Uchida Kazuyuki K Nakayama Hiroyuki H

The Journal of veterinary medical science 20200713 9

Wnt/beta-catenin signaling, E-cadherin and p53 reportedly play important roles in the development and/or progression of human gastrointestinal cancer. The present study evaluated the roles of beta-catenin, E-cadherin and p53 in canine gastrointestinal tumors. Endoscopic biopsy or surgically resected samples, a total of 131, including 38 gastric, 13 small intestinal and 80 large intestinal tumors, were obtained from 95 dogs. Those specimens were examined pathologically. Immunohistochemically, nuc ...[more]

PMID: 32655099

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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:Evaluation for malignancy of the adrenal cortex, adrenal cortical carcinoma (ACC), is a challenge in surgical pathology due to its relative rarity and histologic overlap with its benign counterpart, adrenocortical adenoma (ACA). We characterized a cohort of human ACC and ACA, including a molecular screen, with a goal of identifying potential diagnostic adjuncts. Thirty-six cases of ACC underwent histologic and clinical review. In the 31 ACC cases with available material and a cohort of 10 ACA cases, a multiplex nucleotide amplification molecular screen from formalin-fixed, paraffin-embedded tissue was peformed. ACCs demonstrated a wide variety of clinical and histologic characteristics with overall poor but unpredictable survival for subjects with ACC. By mutational screen, 12/31 (38.7%) carcinomas harbored CTNNB1 mutations, 1 with an additional TP53 mutation; 1 case each had isolated APC and TP53 mutations; 16 were wild-type for all tested loci; and 1 case demonstrated repeated assay failures. Two of the 10 ACA (20%) demonstrated CTNNB1 mutations by mutational screen, with no additional mutations. Immunohistochemistry for beta-catenin was performed and compared with the results of the molecular screen. Strong nuclear beta-catenin immunopositivity corresponded to the presence of CTNNB1 mutation by genotyping in 10 of 12 cases (83% sensitivity); the mismatched case(s) demonstrated strong membranous staining by immunohistochemistry. Seventeen of the 18 cases without CTNNB1 mutation showed membranous staining or did not stain (94% specificity); the mismatched case demonstrated scattered (<10%) positive nuclei. Both mutations in ACA were corroborated with immunohistochemistry for beta-catenin. No histomorphologic parameter appeared dominant in lesions with a particular mutational status. Based on these results, mutational status of CTNNB1 in adrenal cortical neoplasms can be predicted with reasonable accuracy by immunohistochemical cellular localization. Nuclear localization of beta-catenin by immunostain may be helpful in analysis of select lesions of the adrenal cortex whose biological behavior is uncertain from clinical and histologic information; a larger cohort is required to test this hypothesis.

Dataset Information

Immunohistochemical analysis of beta-catenin, E-cadherin and p53 in canine gastrointestinal epithelial tumors.

Publications

Immunohistochemical analysis of beta-catenin, E-cadherin and p53 in canine gastrointestinal epithelial tumors.

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