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Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas

1
Laboklin GmbH & Co. KG, 97688 Bad Kissingen, Germany
2
Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany
*
Author to whom correspondence should be addressed.
Vet. Sci. 2019, 6(1), 31; https://doi.org/10.3390/vetsci6010031
Received: 20 December 2018 / Revised: 11 March 2019 / Accepted: 13 March 2019 / Published: 19 March 2019
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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. View Full-Text
Keywords: dog; terrier; urothelial carcinoma; histological grading; BRAF mutation; COX-2 dog; terrier; urothelial carcinoma; histological grading; BRAF mutation; COX-2
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Grassinger, J.M.; Merz, S.; Aupperle-Lellbach, H.; Erhard, H.; Klopfleisch, R. Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas. Vet. Sci. 2019, 6, 31.

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