BRAF-V600E Protein Expression in Canine Malignant Cutaneous Melanoma, in Accordance with the Introduction of Biomarkers in Comparative Oncology Studies

Hossein Mehrani, S. Yasini, A. Muhammadnejad, Seyed Hamed Shirazi Beheshtiha
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Abstract

Background: Melanoma is the cause of death for 1.3% of all cancer patients in humans. The key role of the 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 the 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-μmthick 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 improving treatment options, using dogs as an animal model in human melanoma clinical trials, and possibly identifying a new prognostic biomarker in canine melanoma.
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犬恶性皮肤黑色素瘤中的 BRAF-V600E 蛋白表达与肿瘤比较研究中生物标记物的引入相一致
背景:黑色素瘤是1.3%的人类癌症患者死亡的原因。BRAF蛋白在人类黑色素瘤进展中的关键作用已被证实,其预后意义已被揭示。由于犬癌在生物学行为和分子异常方面与人类癌症相似,BRAF蛋白可能在犬黑色素瘤中表达,与人类黑色素瘤相同。尽管在犬黑色素瘤中研究了BRAF突变,但在犬皮肤黑色素瘤中BRAF蛋白水平的状态尚未被研究。方法:随机选取32例经福尔马林固定、石蜡包埋的犬恶性皮肤黑色素瘤组织标本。将样品切成3 μm厚的切片,采用免疫组化和抗BRAF V600E (VE1)小鼠单克隆抗体检测BRAF蛋白表达。32例样本中21例阴性,11例BRAF蛋白高表达。结论:在34.3%的犬皮肤黑色素瘤样本中检测到BRAF阳性表达,可能是改善治疗方案的一步,可以将狗作为人类黑色素瘤临床试验的动物模型,并可能发现犬黑色素瘤的新的预后生物标志物。
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