Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas
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), histologi...
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| Format: | Article |
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MDPI AG
2019-03-01
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| Series: | Veterinary Sciences |
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| Online Access: | http://www.mdpi.com/2306-7381/6/1/31 |
| _version_ | 1818560529035165696 |
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| author | Julia M. Grassinger Sophie Merz Heike Aupperle-Lellbach Hanna Erhard Robert Klopfleisch |
| author_facet | Julia M. Grassinger Sophie Merz Heike Aupperle-Lellbach Hanna Erhard Robert Klopfleisch |
| author_sort | Julia M. Grassinger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T00:39:33Z |
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| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-12-14T00:39:33Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-bd067a443f594c34ae55122cf70fcf872022-12-21T23:24:27ZengMDPI AGVeterinary Sciences2306-73812019-03-01613110.3390/vetsci6010031vetsci6010031Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell CarcinomasJulia M. Grassinger0Sophie Merz1Heike Aupperle-Lellbach2Hanna Erhard3Robert Klopfleisch4Laboklin GmbH & Co. KG, 97688 Bad Kissingen, GermanyInstitute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, GermanyLaboklin GmbH & Co. KG, 97688 Bad Kissingen, GermanyLaboklin GmbH & Co. KG, 97688 Bad Kissingen, GermanyInstitute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, GermanyThe 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.http://www.mdpi.com/2306-7381/6/1/31dogterrierurothelial carcinomahistological gradingBRAF mutationCOX-2 |
| spellingShingle | Julia M. Grassinger Sophie Merz Heike Aupperle-Lellbach Hanna Erhard Robert Klopfleisch Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas Veterinary Sciences dog terrier urothelial carcinoma histological grading BRAF mutation COX-2 |
| title | Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas |
| title_full | Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas |
| title_fullStr | Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas |
| title_full_unstemmed | Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas |
| title_short | Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas |
| title_sort | correlation of braf variant v595e breed histological grade and cyclooxygenase 2 expression in canine transitional cell carcinomas |
| topic | dog terrier urothelial carcinoma histological grading BRAF mutation COX-2 |
| url | http://www.mdpi.com/2306-7381/6/1/31 |
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