Abstract
The presence of BRAF variant V595E, as well as an increased cyclooxygenase-2 (COX-2) expression in canine transitional cell carcinoma (TCC) are well-described in the literature. The aim of the present study was to investigate the correlation between breed (terrier versus non-terrier dogs), histological grade, COX-2 expression, and BRAF mutation in canine TCC. Therefore, transmural TCC biopsies from 65 dogs (15 terriers, 50 non-terriers) were graded histologically into low- and high-grade. Immunohistochemical evaluation of the intensity of COX-2 expression was performed using an immunoreactive score (IRS). Exon 15 of chromosome 16 was examined for the BRAF variant c.1799T>A by TaqMan® SNP assay. TCC was low-grade in 20 cases (one terrier, 19 non-terriers) and high-grade in 45 cases (14 terriers, 31 non-terriers). Contrary to humans, histological grade was not significantly correlated to the intensity of COX-2 expression. BRAF mutation was detected in 11/15 (73%) TCC of terriers and in 18/50 (36%) TCC of non-terriers. Histological grade and BRAF mutation were not correlated significantly (p = 0.2912). Terriers had a considerably higher prevalence of high-grade tumors (p < 0.0001), as well as of BRAF mutation (p ≤ 0.05) compared to non-terriers. In non-terriers, neoplasms with BRAF mutation showed a significantly higher intensity of COX-2 expression than those without BRAF mutation (p ≤ 0.05). In conclusion, in contrast to humans, testing for BRAF mutation in canine TCC is a sensitive diagnostic method especially in terriers (73%) and may be recommended as a screening test. However, evidence of BRAF mutation in canine TCC is not a predictor for the histological grade. Moreover, a positive correlation between histological grade and the intensity of COX-2 expression was not found. Further studies are necessary to clarify the clinical and prognostic relevance of the elevated intensity of COX-2 expression of TCC with BRAF mutation detected in non-terriers.
Highlights
Transitional cell carcinoma (TCC), referred to as urothelial carcinoma, is the most common malignant tumor of the canine urinary tract
To the authors’ knowledge, this is the first study in dogs investigating the histological grade of transitional cell carcinoma (TCC), the intensity of COX-2 expression, and the presence of the BRAF mutation with a special focus on breed predilection of terriers
We found no considerable difference in the intensity of COX-2 expression between low- and high-grade canine TCC
Summary
Transitional cell carcinoma (TCC), referred to as urothelial carcinoma, is the most common malignant tumor of the canine urinary tract. The breed-associated risk includes a 21-fold increased risk in Scottish terriers and a 3.0–6.5-fold increased risk in Eskimo dogs, Shetland sheepdogs, West. Keeshonds, samoyeds, and beagles compared to mixed breed dogs [1]. The mean age of dogs at time of diagnosis is 11 years [2]. Several studies have confirmed the increased risk of bladder cancer in female dogs and in neutered ones compared to intact dogs of the same gender [3]. In dogs with high breed-associated risk, the sex predilection is.
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