Immunohistochemical expression of β-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas

Abstract

Background Inflammation 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). Results The 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). Conclusions β-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.

Bridging the Species Gap: Morphological and Molecular Comparison of Feline and Human Intestinal Carcinomas

“…From a comparative point of view, in intestinal neoplasms in dogs, CTNNB1 mutations were proven to be more often causative than APC mutations, with CTNNB1 being mutated in >60% of canine colorectal tumors [ 22 ]. Several studies also provide evidence of nuclear β-catenin translocation and accumulation in canine intestinal adenomas and carcinomas [ 37 , 38 , 39 ].…”

Tumor-associated macrophages: Prognostic and therapeutic targets for cancer in humans and dogs

“…These authors suggest this may be due in part to the unique properties of bone, namely that cytokines responsible for M2 differentiation can also inhibit osteoclast formation ( 170 ). In canine colorectal cancer, one study found no significant difference in macrophage counts between control tissue, adenomas, and carcinomas, while another found lower levels of macrophages in adenomas and carcinomas as compared to controls ( 144 , 145 ).…”

Histopathological and Immunohistochemical Characterization of Sebaceous Adenoma and Epithelioma in Dogs

“…IHC was conducted using antibodies against rabbit polyclonal Ki-67 (ab15580; Abcam, Waltham, MA, USA), previously used in canine tissues [15,16]. After deparaffinizing and rehydration with xylene and alcohol, slides were washed under tap water for 10 min.…”