BRAF-V600E Protein Expression in Canine Malignant Cutaneous Melanoma, in Accordance with the Introduction of Biomarkers in Comparative Oncology Studies
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Abstract
Background: Melanoma is the cause of death of 1.3% of all cancer patients in humans. The key role of BRAF protein in the progression of human melanoma has been confirmed and its prognostic significance has been revealed. Because canine cancer resembles human cancer in biological behavior and molecular abnormalities, BRAF protein may be expressed in canine melanoma, the same as human melanoma. despite the investigation of BRAF mutation in canine melanoma, the status of BRAF at the protein level in canine skin melanoma has not yet been examined. Methods: Thirty-two formalin-fixed, paraffin-embedded tissue samples of canine malignant cutaneous melanoma were randomly selected. After cutting into 3-μm-thick sections, the samples were evaluated for BRAF protein expression by immunohistochemistry and using the anti-BRAF V600E (VE1) mouse monoclonal antibody. Results: The BRAF status was assessed using the Allred scoring system. Among the 32 samples examined, 21 samples were negative and 11 cases showed high BRAF protein expression. Conclusion: The detection of positive BRAF expression in 34.3% of canine cutaneous melanoma samples could be a step forward to improve treatment options, use the dog as an animal model in human melanoma clinical trials, and possibly identify a new prognostic biomarker in canine melanoma.
Refianti, R., A.B. Mutiara, and R.P. Priyandini, Classification of melanoma skin cancer using convolutional neural network. International Journal of Advanced Computer Science and Applications, 2019. 10(3).
2. Teixeira, T.F., et al., Retrospective study of melanocytic neoplasms in dogs and cats. Braz. J. Vet. Pathol, 2010. 3(2): p. 100-104.
3. https://seer.cancer.gov/statfacts/html/melan.html.
4. Surendre, R., et al., Malignant cutaneous melanoma in a shih tzu mix: A case report. J. Anim. Health Prod, 2021. 9(1): p. 47-51.
5. DeLeon, M., Cutaneous Melanoma: A Comparative Study Between Gray Horses, Canines, and Humans. 2021.
6. Alcalá, A.M. and K.T. Flaherty, BRAF inhibitors for the treatment of metastatic melanoma: clinical trials and mechanisms of resistance. Clinical cancer research, 2012. 18(1): p. 33-39.
7. Mochizuki, H. and M. Breen, Comparative aspects of BRAF mutations in canine cancers. Veterinary Sciences, 2015. 2(3): p. 231-245.
8. Bollag, G., et al., Vemurafenib: the first drug approved for BRAF-mutant cancer. Nature reviews Drug discovery, 2012. 11(11): p. 873-886.
9. Welsh, S.J. and P.G. Corrie, Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Therapeutic advances in medical oncology, 2015. 7(2): p. 122-136.
10. Safaee Ardekani, G., et al., Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma. British Journal of Dermatology, 2013. 169(2): p. 320-328.
11. Dhillon, A.S., et al., MAP kinase signalling pathways in cancer. Oncogene, 2007. 26(22): p. 3279-3290.
12. Fowles, J., C. Denton, and D. Gustafson, Comparative analysis of MAPK and PI3K/AKT pathway activation and inhibition in human and canine melanoma. Veterinary and comparative oncology, 2015. 13(3): p. 288-304.
13. Shelly, S., et al., Exon 15 BRAF mutations are uncommon in canine oral malignant melanomas. Mammalian Genome, 2005. 16(3): p. 211-217.
14. Mochizuki, H., et al., BRAF mutations in canine cancers. PloS one, 2015. 10(6): p. e0129534.
15. Vieites, B., et al., CK19 expression in breast tumours and lymph node metastasis after neoadjuvant therapy. Histopathology, 2016. 69(2): p. 239-249.
16. Lin, A., et al., The effect of local non‐thermal plasma therapy on the cancer‐immunity cycle in a melanoma mouse model. Bioengineering & Translational Medicine, 2022: p. e10314.
17. Chapman, P.B., et al., Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine, 2011. 364(26): p. 2507-2516.
18. Shi, H., et al., Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor TherapyCore Resistance Mechanisms and Genetic Evolution of Melanoma under BRAF Inhibitor Selection. Cancer discovery, 2014. 4(1): p. 80-93.
19. Hugdahl, E., et al., BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival. British journal of cancer, 2016. 114(7): p. 801-808.
20. Nishiya, A.T., et al., Comparative aspects of canine melanoma. Veterinary sciences, 2016. 3(1): p. 7.
21. Maldonado, J.L., et al., Determinants of BRAF mutations in primary melanomas. Journal of the National Cancer Institute, 2003. 95(24): p. 1878-1890.
22. Edwards, R., et al., Absence of BRAF mutations in UV-protected mucosal melanomas. Journal of medical genetics, 2004. 41(4): p. 270-272.
23. Capper, D., et al., Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta neuropathologica, 2011. 122(1): p. 11-19.
24. Pinho, S.S., et al., Canine tumors: a spontaneous animal model of human carcinogenesis. Translational Research, 2012. 159(3): p. 165-172.
25. Prouteau, A. and C. André, Canine melanomas as models for human melanomas: clinical, histological, and genetic comparison. Genes, 2019. 10(7): p. 501.
26. Tarone, L., et al., Naturally occurring cancers in pet dogs as pre-clinical models for cancer immunotherapy. Cancer Immunology, Immunotherapy, 2019. 68(11): p. 1839-1853.
27. Gordon, I., et al., The Comparative Oncology Trials Consortium: using spontaneously occurring cancers in dogs to inform the cancer drug development pathway. PLoS medicine, 2009. 6(10): p. e1000161.
28. Cekanova, M. and K. Rathore, Animal models and therapeutic molecular targets of cancer: utility and limitations. Drug design, development and therapy, 2014. 8: p. 1911.
29. Abadie, J., et al., Canine invasive mammary carcinomas as models of human breast cancer. Part 2: immunophenotypes and prognostic significance. Breast cancer research and treatment, 2018. 167(2): p. 459-468.
30. Abu-Helil, B. and L. van der Weyden, Metastasis in the wild: investigating metastasis in non-laboratory animals. Clinical & Experimental Metastasis, 2019. 36(1): p. 15-28.
31. Karkare, S., et al., Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors. Scientific reports, 2019. 9(1): p. 1-10.
2. Teixeira, T.F., et al., Retrospective study of melanocytic neoplasms in dogs and cats. Braz. J. Vet. Pathol, 2010. 3(2): p. 100-104.
3. https://seer.cancer.gov/statfacts/html/melan.html.
4. Surendre, R., et al., Malignant cutaneous melanoma in a shih tzu mix: A case report. J. Anim. Health Prod, 2021. 9(1): p. 47-51.
5. DeLeon, M., Cutaneous Melanoma: A Comparative Study Between Gray Horses, Canines, and Humans. 2021.
6. Alcalá, A.M. and K.T. Flaherty, BRAF inhibitors for the treatment of metastatic melanoma: clinical trials and mechanisms of resistance. Clinical cancer research, 2012. 18(1): p. 33-39.
7. Mochizuki, H. and M. Breen, Comparative aspects of BRAF mutations in canine cancers. Veterinary Sciences, 2015. 2(3): p. 231-245.
8. Bollag, G., et al., Vemurafenib: the first drug approved for BRAF-mutant cancer. Nature reviews Drug discovery, 2012. 11(11): p. 873-886.
9. Welsh, S.J. and P.G. Corrie, Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Therapeutic advances in medical oncology, 2015. 7(2): p. 122-136.
10. Safaee Ardekani, G., et al., Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma. British Journal of Dermatology, 2013. 169(2): p. 320-328.
11. Dhillon, A.S., et al., MAP kinase signalling pathways in cancer. Oncogene, 2007. 26(22): p. 3279-3290.
12. Fowles, J., C. Denton, and D. Gustafson, Comparative analysis of MAPK and PI3K/AKT pathway activation and inhibition in human and canine melanoma. Veterinary and comparative oncology, 2015. 13(3): p. 288-304.
13. Shelly, S., et al., Exon 15 BRAF mutations are uncommon in canine oral malignant melanomas. Mammalian Genome, 2005. 16(3): p. 211-217.
14. Mochizuki, H., et al., BRAF mutations in canine cancers. PloS one, 2015. 10(6): p. e0129534.
15. Vieites, B., et al., CK19 expression in breast tumours and lymph node metastasis after neoadjuvant therapy. Histopathology, 2016. 69(2): p. 239-249.
16. Lin, A., et al., The effect of local non‐thermal plasma therapy on the cancer‐immunity cycle in a melanoma mouse model. Bioengineering & Translational Medicine, 2022: p. e10314.
17. Chapman, P.B., et al., Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine, 2011. 364(26): p. 2507-2516.
18. Shi, H., et al., Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor TherapyCore Resistance Mechanisms and Genetic Evolution of Melanoma under BRAF Inhibitor Selection. Cancer discovery, 2014. 4(1): p. 80-93.
19. Hugdahl, E., et al., BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival. British journal of cancer, 2016. 114(7): p. 801-808.
20. Nishiya, A.T., et al., Comparative aspects of canine melanoma. Veterinary sciences, 2016. 3(1): p. 7.
21. Maldonado, J.L., et al., Determinants of BRAF mutations in primary melanomas. Journal of the National Cancer Institute, 2003. 95(24): p. 1878-1890.
22. Edwards, R., et al., Absence of BRAF mutations in UV-protected mucosal melanomas. Journal of medical genetics, 2004. 41(4): p. 270-272.
23. Capper, D., et al., Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta neuropathologica, 2011. 122(1): p. 11-19.
24. Pinho, S.S., et al., Canine tumors: a spontaneous animal model of human carcinogenesis. Translational Research, 2012. 159(3): p. 165-172.
25. Prouteau, A. and C. André, Canine melanomas as models for human melanomas: clinical, histological, and genetic comparison. Genes, 2019. 10(7): p. 501.
26. Tarone, L., et al., Naturally occurring cancers in pet dogs as pre-clinical models for cancer immunotherapy. Cancer Immunology, Immunotherapy, 2019. 68(11): p. 1839-1853.
27. Gordon, I., et al., The Comparative Oncology Trials Consortium: using spontaneously occurring cancers in dogs to inform the cancer drug development pathway. PLoS medicine, 2009. 6(10): p. e1000161.
28. Cekanova, M. and K. Rathore, Animal models and therapeutic molecular targets of cancer: utility and limitations. Drug design, development and therapy, 2014. 8: p. 1911.
29. Abadie, J., et al., Canine invasive mammary carcinomas as models of human breast cancer. Part 2: immunophenotypes and prognostic significance. Breast cancer research and treatment, 2018. 167(2): p. 459-468.
30. Abu-Helil, B. and L. van der Weyden, Metastasis in the wild: investigating metastasis in non-laboratory animals. Clinical & Experimental Metastasis, 2019. 36(1): p. 15-28.
31. Karkare, S., et al., Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors. Scientific reports, 2019. 9(1): p. 1-10.
| Files | ||
| Issue | Vol 14 No 2 (2022) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v14i2.14377 | |
| Keywords | ||
| immunohistochemistry BRAF canine cutaneous melanoma protein expression | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Muhammadnejad A, Mehrani H, Yasini SP, Shirazi Beheshtiha SH. BRAF-V600E Protein Expression in Canine Malignant Cutaneous Melanoma, in Accordance with the Introduction of Biomarkers in Comparative Oncology Studies. Basic Clin Cancer Res. 2023;14(2):95-101.
