{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:10:17Z","timestamp":1768349417600,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Albert Heim Foundation","award":["148"],"award-info":[{"award-number":["148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Alterations of the BRAF gene and the resulting changes in the BRAF protein are one example of molecular cancer profiling in humans and dogs. We tested 227 samples of canine carcinomas from different anatomical sites (anal sac (n = 23), intestine (n = 21), liver (n = 21), lungs (n = 19), mammary gland (n = 20), nasal cavity (n = 21), oral epithelium (n = 18), ovary (n = 20), prostate (n = 21), thyroid gland (n = 21), urinary bladder (n = 22)) with two commercially available primary anti-BRAFV600E antibodies (VE1 Ventana, VE1 Abcam). The immunohistochemical results were confirmed with droplet digital PCR (ddPCR). BRAFV595E-mutated cases were found in canine prostatic (16\/21), urothelial (17\/22), and oral squamous cell carcinomas (4\/18), while other carcinoma types tested negative. Both antibodies showed consistent results, with intracytoplasmic immunolabeling of tumour cells, making them reliable tools for detecting the BRAFV595E mutation in canine carcinomas. In conclusion, identifying BRAF mutations from biopsy material offers a valuable opportunity to enhance cancer treatment strategies (BRAF inhibitors) in canine urothelial carcinomas, prostatic carcinomas, and oral squamous cell carcinomas.<\/jats:p>","DOI":"10.3390\/vetsci11110584","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T07:02:58Z","timestamp":1732086178000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expression of Mutated BRAFV595E Kinase in Canine Carcinomas\u2014An Immunohistochemical Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Annika","family":"Bartel","sequence":"first","affiliation":[{"name":"LABOKLIN GmbH & Co. KG, 97688 Bad Kissingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4601-1480","authenticated-orcid":false,"given":"Heike","family":"Aupperle-Lellbach","sequence":"additional","affiliation":[{"name":"LABOKLIN GmbH & Co. KG, 97688 Bad Kissingen, Germany"},{"name":"School of Medicine, Institute of Pathology, Technical University of Munich, Trogerstr. 18, 80333 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-0713","authenticated-orcid":false,"given":"Alexandra","family":"Kehl","sequence":"additional","affiliation":[{"name":"LABOKLIN GmbH & Co. KG, 97688 Bad Kissingen, Germany"},{"name":"School of Medicine, Institute of Pathology, Technical University of Munich, Trogerstr. 18, 80333 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Weidle","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Pathology, Technical University of Munich, Trogerstr. 18, 80333 M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonore","family":"Aeschlimann","sequence":"additional","affiliation":[{"name":"Institute of Animal Pathology, COMPATH, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6308-0568","authenticated-orcid":false,"given":"Robert","family":"Klopfleisch","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Free University of Berlin, 14195 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3049-0103","authenticated-orcid":false,"given":"Simone de","family":"Brot","sequence":"additional","affiliation":[{"name":"Institute of Animal Pathology, COMPATH, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dhein, E.S., Heikkil\u00e4, U., Oevermann, A., Blatter, S., Meier, D., Hartnack, S., and Guscetti, F. (2024). Incidence rates of the most common canine tumors based on data from the Swiss Canine Cancer Registry (2008 to 2020). PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0302231"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jcpa.2022.07.009","article-title":"Tumour Incidence in Dogs in Germany: A Retrospective Analysis of 109,616 Histopathological Diagnoses (2014\u20132019)","volume":"198","author":"Grassinger","year":"2022","journal-title":"J. Comp. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41392-024-01823-2","article-title":"Tumor biomarkers for diagnosis, prognosis and targeted therapy","volume":"9","author":"Zhou","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Aupperle-Lellbach, H., Kehl, A., de Brot, S., and van der Weyden, L. (2024). Clinical Use of Molecular Biomarkers in Canine and Feline Oncology: Current and Future. Vet. Sci., 11.","DOI":"10.3390\/vetsci11050199"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.21037\/pcm-20-39","article-title":"A narrative review of BRAF alterations in human tumors: Diagnostic and predictive implications","volume":"3","author":"Sholl","year":"2020","journal-title":"Precis. Cancer Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbrc.2010.07.092","article-title":"RAF protein-serine\/threonine kinases: Structure and regulation","volume":"399","author":"Roskoski","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Esteban-Villarrubia, J., Soto-Castillo, J.J., Pozas, J., San Rom\u00e1n-Gil, M., Orejana-Mart\u00edn, I., Torres-Jim\u00e9nez, J., Carrato, A., Alonso-Gordoa, T., and Molina-Cerrillo, J. (2020). Tyrosine Kinase Receptors in Oncology. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228529"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc969","article-title":"Targeting RAS signalling pathways in cancer therapy","volume":"3","author":"Downward","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1038\/sj.onc.1210421","article-title":"MAP kinase signalling pathways in cancer","volume":"26","author":"Dhillon","year":"2007","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S0092-8674(04)00215-6","article-title":"Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF","volume":"116","author":"Wan","year":"2004","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mochizuki, H., Kennedy, K., Shapiro, S.G., and Breen, M. (2015). BRAF Mutations in Canine Cancers. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129534"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1158\/1541-7786.MCR-14-0689","article-title":"Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer\u2014Evidence for a Relevant Model System and Urine-Based Diagnostic Test","volume":"13","author":"Decker","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3390\/vetsci2030231","article-title":"Comparative Aspects of BRAF Mutations in Canine Cancers","volume":"2","author":"Mochizuki","year":"2015","journal-title":"Vet. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/vco.12275","article-title":"Sequence analysis of RAS and RAF mutation hot spots in canine carcinoma","volume":"15","author":"Mochizuki","year":"2017","journal-title":"Vet. Comp. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.tvjl.2015.01.017","article-title":"Management of transitional cell carcinoma of the urinary bladder in dogs: A review","volume":"205","author":"Fulkerson","year":"2015","journal-title":"Vet. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/vco.12869","article-title":"Highly recurrent BRAF p.V595E mutation in canine papillary oral squamous cell carcinoma","volume":"21","author":"Peralta","year":"2023","journal-title":"Vet. Comp. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1056\/NEJMoa1103782","article-title":"Improved survival with vemurafenib in melanoma with BRAF V600E mutation","volume":"364","author":"Chapman","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1158\/1535-7163.MCT-20-0893","article-title":"Phase I\/II Trial of Vemurafenib in Dogs with Naturally Occurring, BRAF-mutated Urothelial Carcinoma","volume":"20","author":"Rossman","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/01652176.2021.1905194","article-title":"Longitudinal assessment of B-RAF V595E levels in the peripheral cell-free tumor DNA of a 10-year-old spayed female Korean Jindo dog with unresectable metastatic urethral transitional cell carcinoma for monitoring the treatment response to a RAF inhibitor (sorafenib)","volume":"41","author":"Kim","year":"2021","journal-title":"Vet. Q."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/modpathol.2012.168","article-title":"Immunohistochemistry with a mutation-specific monoclonal antibody as a screening tool for the BRAFV600E mutational status in primary cutaneous malignant melanoma","volume":"26","author":"Feller","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/his.12154","article-title":"Immunohistochemistry using the BRAF V600E mutation-specific monoclonal antibody VE1 is not a useful surrogate for genotyping in colorectal adenocarcinoma","volume":"63","author":"Adackapara","year":"2013","journal-title":"Histopathology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s00401-013-1118-5","article-title":"VE1 immunohistochemistry in pituitary adenomas is not associated with BRAF V600E mutation","volume":"125","author":"Sperveslage","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/vco.12978","article-title":"Effective detection of BRAF(V595E) mutation in canine urothelial and prostate carcinomas using immunohistochemistry","volume":"22","author":"Aeschlimann","year":"2024","journal-title":"Vet. Comp. Oncol."},{"key":"ref_25","unstructured":"(2024, September 22). Anti-BRAF (Mutated V600E) Antibody [VE1] (ab228461)|Abcam. Available online: https:\/\/www.abcam.com\/en-us\/products\/primary-antibodies\/braf-mutated-v600e-antibody-ve1-ab228461#."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Meuten, D.J. (2017). Tumors in Domestic Animals, John Wiley & Sons. [5th ed.].","DOI":"10.1002\/9781119181200"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jcpa.2019.07.005","article-title":"Histopathological Terminology Standards for the Reporting of Prostatic Epithelial Lesions in Dogs","volume":"171","author":"Palmieri","year":"2019","journal-title":"J. Comp. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4103\/0256-4947.51806","article-title":"Tissue Microarray: A rapidly evolving diagnostic and research tool","volume":"29","author":"Jawhar","year":"2009","journal-title":"Ann. Saudi Med."},{"key":"ref_29","unstructured":"(2024, September 22). ROCHE\u2014eLabDoc. Available online: https:\/\/elabdoc-prod.roche.com\/eLD\/web\/global\/en\/products\/RTD001191."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/PAI.0000000000000069","article-title":"Standardization of negative controls in diagnostic immunohistochemistry: Recommendations from the international ad hoc expert panel","volume":"22","author":"Torlakovic","year":"2014","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mochizuki, H., Shapiro, S.G., and Breen, M. (2015). Detection of BRAF Mutation in Urine DNA as a Molecular Diagnostic for Canine Urothelial and Prostatic Carcinoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144170"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.21037\/pcm.2019.09.04","article-title":"Precision medicine: BRAF mutations in thyroid cancer","volume":"2","author":"Podolski","year":"2019","journal-title":"Precis. Cancer Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yan, N., Guo, S., Zhang, H., Zhang, Z., Shen, S., and Li, X. (2022). BRAF-Mutated Non-Small Cell Lung Cancer: Current Treatment Status and Future Perspective. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.863043"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Djanani, A., Eller, S., \u00d6fner, D., Troppmair, J., and Maglione, M. (2020). The Role of BRAF in Metastatic Colorectal Carcinoma\u2013Past, Present, and Future. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239001"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gnoni, A., Licchetta, A., Memeo, R., Argentiero, A., Solimando, A.G., Longo, V., Delcuratolo, S., and Brunetti, O. (2019). Role of BRAF in Hepatocellular Carcinoma: A Rationale for Future Targeted Cancer Therapies. Medicina, 55.","DOI":"10.3390\/medicina55120754"},{"key":"ref_36","first-page":"415","article-title":"Molecular Status of BRAF Mutation in Prostate Adenocarcinoma: The Analysis of 100 Cases in North-East of IRAN","volume":"13","author":"Jafarian","year":"2018","journal-title":"Iran. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/vco.12997","article-title":"Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours","volume":"22","author":"Kuroki","year":"2024","journal-title":"Vet. Comp. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1177\/03009858231217242","article-title":"Diagnostic challenge in veterinary pathology: Detection of BRAFV595E mutation in a dog with follicular cystitis and flat urothelial lesion with atypia","volume":"61","author":"Chambers","year":"2024","journal-title":"Vet. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"537","DOI":"10.5858\/2010-0702-RAIR.1","article-title":"Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin-embedded tissue","volume":"135","author":"Engel","year":"2011","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gohar, F., Gohar, A., H\u00fclskamp, G., and Debus, O. (2018). The Translational Medicine Professional: A Bridge Between Bench and Bedside?. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00294"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gentilini, F., Palgrave, C.J., Neta, M., Tornago, R., Furlanello, T., McKay, J.S., Sacchini, F., and Turba, M.E. (2022). Validation of a Liquid Biopsy Protocol for Canine BRAFV595E Variant Detection in Dog Urine and Its Evaluation as a Diagnostic Test Complementary to Cytology. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.909934"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gibson, E.A., and Culp, W.T.N. (2024). Canine Prostate Cancer: Current Treatments and the Role of Interventional Oncology. Vet. Sci., 11.","DOI":"10.3390\/vetsci11040169"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100788","DOI":"10.1016\/j.esmoop.2023.100788","article-title":"Precision oncology for BRAF-mutant cancers with BRAF and MEK inhibitors: From melanoma to tissue-agnostic therapy","volume":"8","author":"Gouda","year":"2023","journal-title":"ESMO Open"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/bjh.12201","article-title":"Rapid response of biallelic BRAF V600E mutated hairy cell leukaemia to low dose vemurafenib","volume":"161","author":"Follows","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s11523-020-00727-9","article-title":"Molecular Targeting of a BRAF Mutation in Pancreatic Ductal Adenocarcinoma: Case Report and Literature Review","volume":"15","author":"Seghers","year":"2020","journal-title":"Target. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/nature09627","article-title":"COT drives resistance to RAF inhibition through MAP kinase pathway reactivation","volume":"468","author":"Johannessen","year":"2010","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1056\/NEJMoa1210093","article-title":"Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations","volume":"367","author":"Flaherty","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Jung, H., Bae, K., Lee, J.Y., Kim, J.-H., Han, H.-J., Yoon, H.-Y., and Yoon, K.-A. (2021). Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179151"},{"key":"ref_49","first-page":"97","article-title":"Tolerability of oral sorafenib in pet dogs with a diagnosis of cancer","volume":"8","author":"Foskett","year":"2017","journal-title":"Vet. Med."}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/11\/11\/584\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:35:36Z","timestamp":1760114136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/11\/11\/584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":49,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["vetsci11110584"],"URL":"https:\/\/doi.org\/10.3390\/vetsci11110584","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}