Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?
Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?
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DOI：
10.1007/s13277-015-3661-2
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发表时间：
2015-11-01
期刊：
影响因子：
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通讯作者：
Antuofermo, E.
中科院分区：
文献类型：
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作者：
Burrai, G. P.;Tanca, A.;Antuofermo, E.
犬乳腺肿瘤(CMTs)与人类乳腺癌(HBC)有许多共同之处，尤其是与癌症相关的途径。尽管人表皮生长因子受体2(HER2)在HBC中发挥着重要的治疗和预后生物标志物的作用，但其在CMT的发病机制和预后中的相关性仍存在争议。本研究的目的是研究HER2在犬乳腺增生症和肿瘤组织中的表达，并用多种分子方法评价最常用的抗HER2多克隆抗体的特异性。用免疫组织化学(IHC)和实时定量聚合酶链式反应(QRT)检测HER2蛋白和RNA的表达。免疫组化显示22%的癌细胞胞膜较厚，并伴有非特异性胞浆染色。与正常乳腺组织相比，腺瘤和癌组织中HER2基因的表达显著增加，但在良性肿瘤和恶性肿瘤中的表达没有显著差异。免疫印迹(WB)和反相蛋白阵列(RPPA)进一步证实，IHC结果表明FDA批准的抗体在CMT样本中缺乏特异性。此外，在IHC调查中，在一例表达蛋白质的肿瘤中没有通过质谱仪(MS)检测到HER2。这项研究强调，当试图将与癌症相关的生物标志物和途径的信息从人类转化为兽医时，需要谨慎行事。需要进一步的研究来仔细评估HER2在CMTs中的诊断和生物学作用，以及将犬乳腺肿瘤用作HER2过表达乳腺癌的模型。
Canine mammary tumors (CMTs) share many features with human breast cancer (HBC), specifically concerning cancer-related pathways. Although the human epidermal growth factor receptor 2 (HER2) plays a significant role as a therapeutic and prognostic biomarker in HBC, its relevance in the pathogenesis and prognosis of CMT is still controversial. The aim of this study was to investigate HER2 expression in canine mammary hyperplasic and neoplastic tissues as well as to evaluate the specificity of the most commonly used polyclonal anti HER2 antibody by multiple molecular approaches. HER2 protein and RNA expression were determined by immunohistochemistry (IHC) and by quantitative real-time (qRT) PCR. A strong cell membrane associated with non-specific cytoplasmic staining was observed in 22 % of carcinomas by IHC. Adenomas and carcinomas exhibited a significantly higher HER2 mRNA expression when compared to normal mammary glands, although no significant difference between benign and malignant tumors was noticed by qRT-PCR. The IHC results suggest a lack of specificity of the FDA-approved antibody in CMT samples as further demonstrated by Western immunoblotting (WB) and reverse phase protein arrays (RPPA). Furthemore, HER2 was not detected by mass spectrometry (MS) in a protein-expressing carcinoma at the IHC investigation. This study highlights that caution needs to be used when trying to translate from human to veterinary medicine information concerning cancer-related biomarkers and pathways. Further investigations are necessary to carefully assess the diagnostic and biological role specifically exerted by HER2 in CMTs and the use of canine mammary tumors as a model of HER2 over-expressing breast cancer.