Overexpression and Mutation of p53 Exons 4-8 in Canine Intestinal Adenocarcinoma.

p53 is mutated and overexpressed during malignant transformation, including in human colorectal cancer. This study investigated the overexpression of p53 protein and mutations in the p53 gene in canine intestinal neoplasia (CIN). Immunohistochemical analysis of p53 was carried out in formalin-fixed and paraffin wax-embedded (FFPE) sections of intestinal tissues from 35 dogs with CIN by the standard peroxidase-anti-peroxidase method. Expression of p53 protein in malignant (adenocarcinoma, n = 20) and benign (adenoma and polyp, n = 8) CINs was compared with tissue from negative controls (samples with no proliferation, n = 7). DNA was extracted from FFPE tissue from one control and 13 cases with overexpression of p53, and exons 4-8 were sequenced. p53 expression was higher in malignant than in benign tissues (P = 0.001). Sequencing was successfully performed in nine cases and mutations were confirmed in three of these cases. One non-sense mutation, one missense mutation and one germline mutation were confirmed for the three cases. This study suggests that p53 overexpression can be a prognostic factor for CIN; however, p53 overexpression in CIN may occur through a mechanism distinct from mutations within the p53 exon 4-8 region.

Expression of Oestrogen Receptor, Progesterone Receptor and Akt in Canine Circumanal Gland Tumours.

We investigated the expression of oestrogen receptor alpha (OR-α), progesterone receptor (PR) and Akt in canine circumanal gland tumours. Immunohistochemistry was conducted on seven normal circumanal glands, 30 circumanal gland adenomas and 40 circumanal gland carcinomas. The expression of OR-α and PR was significantly lower in circumanal gland carcinomas than in circumanal gland adenomas. In contrast, the expression of Akt was markedly higher in circumanal gland carcinomas than in circumanal gland adenomas. These results indicate that the progression of canine circumanal gland tumours is influenced by changes in the expression levels of OR-α, PR and Akt. Identifying the molecular mechanisms of canine circumanal gland tumours requires further study.

Analysis of Obesity-Related Factors and their Association with Aromatase Expression in Canine Malignant Mammary Tumours.

This study was designed to investigate the role of obesity in canine malignant mammary tumours (CMMTs), by assessing aromatase expression and the regulatory roles of immune mediators such as cyclo-oxygenase-2 (COX2), prostaglandin E2 (PGE2), nuclear factor kappa beta (NF-κB), hypoxia inducible factor-1α (HIF-1α) and adipokines (i.e. leptin) in lean, optimal body weight, overweight and obese animals. Clinicopathological data, including the breed, body weight, body condition score and age and neutering status, were collected, together with histopathological characteristics (i.e. histological types, grading and lymphatic invasion). To determine the expression of each factor, immunohistochemistry was conducted with 60 samples of malignant CMMTs. CMMTs from overweight and obese animals had significantly elevated levels of PGE2, and aromatase expression correlated significantly with PGE2, NF-κB and leptin expression. However, no significant difference was observed in terms of histopathological characteristics. The results suggest that PGE2, a known obesity-related immune mediator, could be upregulated in CMMTs from overweight and obese animals. In addition, PGE2, NF-κB and leptin influenced the expression of aromatase, as observed in women.

Analysis of Hypoxia-Inducible Factor-1α Expression Relative to Other Key Factors in Malignant Canine Mammary Tumours.

Hypoxia-inducible factor (HIF)-1α plays important physiological roles, but is also of significance in carcinogenesis in man and animals. This study aimed to identify HIF-1α expression in malignant canine mammary tumours (CMTs) and to find correlations with other key factors by using immunohistochemistry (IHC). The histological classification, grading and evaluation of lymphatic invasion were achieved by examining sections stained by haematoxylin and eosin. Determination of molecular subtype, expression of HIF-1α, oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor (HER)-2, Ki67, vascular endothelial growth factor (VEGF) and E-cadherin was evaluated by IHC in 87 samples of malignant CMTs. HIF-1α expression correlated significantly with histological type, grade of cancer, negativity for OR and expression of Ki67 and VEGF. Lymphatic invasion, molecular subtype, PR, HER-2 and E-cadherin levels did not significantly correlate with HIF-1α expression. The results of this study imply that HIF-1α may potentially play a role in increased malignancy of CMTs, as it does in human breast cancer.