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

by Julia M. Grassinger,Sophie Merz,Heike Aupperle-Lellbach,Hanna Erhard and Robert Klopfleisch

Vet. Sci. 2019, 6(1), 31; Published: 19 March 2019



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.

Antiviral therapy

Marschang RE. 2019

Elsevier, St. Louis, Missouri, USA. Pp. 1160-1161


Marschang RE. 2019

In: Divers SJ, Stahl SJ (eds.). Mader’s Reptile and Amphibian Medicine and Surgery, Elsevier, St. Louis, Missouri, USA. Pp. 247-269


Infectious diseases

Marschang RE, Chitty J. 2019

In: Girling SJ, Raiti P (eds.). BSAVA Manual of Reptiles, 3rd Edition. British Small Animal Veterinary Association, Gloucester, UK. Pp. 423-442

Reptarenaviruses in apparently healthy snakes in an Australian zoological collection

Hyndman TH, Marschang RE, Bruce M, Clark P, Vitali SD. 2019

Austr Vet J. 97(4): 93-102.

CMAH genotyping survey for blood types A, B and C (AB) in purpose-bredcats

ANIMAL GENETICS, First published: 10 March 2019
A. Kehl, E. Mueller and U.Giger

In domestic cats, the AB blood group system consists of the three types A, B and C (also called AB). Mismatches can cause acute hemolytic transfusion reactions and hemolysis of the newborn (neonatal isoerythrolysis, NI). As blood types B and C are inherited recessively to A, breeders need to know the genotype to predict blood types in offspring and avoid NI. Several CMAH variants have been described as being associated with the b and ac alleles, and different genotyping schemes exist. Here, we genotyped 2145 cats with the original SNV panel, including SNVs c.142G>A and ∆‐53, and our new scheme, with SNVs c.179G>T, c.268T>A and c.1322delT, to differentiate types A and B and added the SNV for the common ac (c.364C>T). Based upon the new scheme, all samples were assigned the correct genotype. No discordances appeared for the A allele, and new breed‐specific SNVs (c.179G>T, c.1322delT) for the b allele were discovered. Furthermore, the genotypes A/ac (type A), ac/ac (C) and ac/b (C) could be detected. We found the variant c.179G>T in additional breeds: Ragdoll, Siberian, Scottish Fold, Chartreux, Neva Masquerade, British Shorthair and Highlander. Also, the variant c.364C>T was detected in additional breeds: Bengal, British Shorthair, Maine Coon, and Scottish Fold. We conclude that our new SNV panel is superior in genotyping cats than the original SNV panel and assures correct assignments of types A, B and C to assist veterinary clinicians and breeders to recognize, confirm and avoid blood incompatibilities such as acute hemolytic transfusion reactions and NI.