Detection of human epidermal growth factor receptor 2 overexpression in canine anal sac gland carcinoma.

Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the outcome of these patients. In this study, HER2 expression in ASGC was evaluated to investigate its potential as a therapeutic target for canine ASGC. HER2 mRNA expression in surgically resected ASGC tissues was significantly higher than that in normal anal sac tissue. To evaluate the expression of HER2 protein, paraffin-embedded ASGC tissues were immunohistochemically evaluated. Strong and broad staining of HER2 was detected in ASGC tissues, while HER2 was weakly to moderately stained in normal anal sac apocrine glands and squamous epithelia. The degree of HER2 expression in ASGC tissues was scored based on its intensity and positivity (score: 0-3+). Scoring of HER2 expression revealed 6 samples (24%) scored 3+, 14 (56%) scored 2+, and 5 (20%) scored 1+, with no samples scoring 0. In all, 80% of canine ASGC tissues were positive for HER2 (scored ≥2+). Furthermore, putative HER2-overexpressed cells in ASGC were detected with trastuzumab by flow cytometry. These preliminary data may lead to further evaluation of the role of HER2 in canine ASGC as a mechanism of malignancy and as a therapeutic target for HER2-targeted therapy.

DNA Adduct Assessment During Antihormonal Treatment of Perianal Gland Tumors With Tamoxifen in Male Dogs.

BACKGROUND/AIM: Determination of DNA adduct count was performed in mononuclear cells during antihormonal treatment of perianal gland tumors. MATERIALS AND METHODS: Eight- to fifteen-year-old dogs with carcinoma (CAR Group; N=5), epithelioma (EPI Group; N=16) or adenoma (ADE Group; N=24) were used. The control group suffered from perineal hernia or rectal diverticulum (CTR Group; N=25). Blood was collected at baseline, and at one and six months after the beginning of the anti-hormonal treatment with tamoxifen (1 mg/kg of body weight). DNA adduct count was determined using autoradiography. RESULTS: At baseline, DNA adduct count reached the highest value in the CTR Group, and the lowest in the EPI Group (p<0.05). Six-month-long therapy with tamoxifen resulted in a significant increase in the DNA adduct count by 78.7%, 221.5% and 198.3% in the ADE, EPI and CAR groups, respectively (p<0.05). CONCLUSION: Increased DNA adduct formation after long-term administration of tamoxifen shows its genotoxicity.

Perianal melanoma with a BRAF gene mutation in a young Portuguese Roma native.

A case of a young man diagnosed with perianal nodular melanoma with a gene mutation, accompanied by regional and pulmonary metastases on initial presentation, and later on with hepatic and bone involvement, is presented. The patient underwent wide local excision but was unresponsive to dacarbazine. Targeted therapy with vemurafenib had shown clinical improvement for a 5-month duration until he showed signs of disease progression. Just after the shift of adjuvant therapy to ipilimumab, he was diagnosed with multiple cerebral metastases that eventually led to his demise 6 months after initiation of vemurafenib, having had a 12-month survival period from the time of initial melanoma diagnosis.

COX-2 expression in canine anal sac adenocarcinomas and in non-neoplastic canine anal sacs.

Anal sac adenocarcinoma (ASAC) is a clinically significant canine neoplasm characterized by early lymphatic invasion. Up-regulation of cyclooxygenase isoform 2 (COX-2) has been confirmed in several animal and human neoplastic tissues. The aim of the current study was primarily to evaluate COX-2 expression in canine ASAC and compare it to COX-2 expression in non-neoplastic canine anal sac tissue using immunohistochemistry with scoring for percentage positivity and intensity. Twenty-five ASAC samples and 22 normal anal sacs were available for evaluation. All canine ASAC samples and the normal anal sac tissues stained positively for COX-2. However, while normal anal sac tissue showed strong staining of the ductal epithelial cells, ASAC samples showed staining of the neoplastic glandular epithelial cells, with varying percentage positivity and intensity between ASAC samples. COX-2 immunoreactivity of ASAC samples was of low intensity in 52% and high in 12% of the cases; the remaining samples were of intermediate intensity. Seventy-six per cent of the ASAC had over 50% of the neoplastic glandular cells staining positive. These results confirm that COX-2 is expressed in the neoplastic glandular epithelial cells in canine ASAC and suggest a potential role for COX-2 inhibitors in the management of ASAC. Furthermore, the results indicate that COX-2 is expressed in ductal epithelial cells of the normal anal sac.

Canine tumour suppressor gene p53--mutation in a case of adenoma of circumanal glands.

Highly conserved regions of the tumour suppressor gene p53, including the typical human tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were investigated in various canine neoplasms. A mutation CGG-->TGG (arginine-->tryptophan) was detected in codon 249 in an adenoma of the circumanal gland.