Human epidermal growth factor receptor 2 is overexpressed in canine prostate carcinoma

Human epidermal growth factor receptor 2 is overexpressed in canine prostate carcinoma
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DOI:
10.33611/trs.2020-018
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发表时间:
2021
期刊:
Translational and Regulatory Sciences
影响因子:
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通讯作者:
K. Sakai;Y. Shinohara;K. Kaji;T. Yonezawa;Y. Momoi;S. Maeda
K. Sakai;Y. Shinohara;K. Kaji;T. Yonezawa;Y. Momoi;S. Maeda
中科院分区:
其他
文献类型:
--
作者:
K. Sakai;Y. Shinohara;K. Kaji;T. Yonezawa;Y. Momoi;S. Maeda

文献摘要

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人表皮生长因子受体2(HER 2)是属于HER家族的细胞表面受体酪氨酸激酶。在人类前列腺癌中经常观察到HER 2过表达;然而,没有关于犬前列腺癌(PC)中HER 2表达的报道。本研究的目的是研究犬PC中HER 2的表达及其潜在的分子机制。21福尔马林固定石蜡包埋的犬前列腺组织(13个癌和8个正常对照)的HER 2表达进行了分析,使用免疫组化。应用数字聚合酶链反应技术检测8例前列腺癌和6例正常前列腺组织中HER 2基因的拷贝数。8/13例(61.5%)PC患者出现HER 2过度表达,而正常对照组无HER 2过度表达。HER 2过表达与PC病例的临床特征,如年龄、中性状态、淋巴结受累、远处转移和总生存率之间无显著相关性。在3/8例(37.5%)PC病例中检测到HER 2拷贝数增加(CNG),但在正常对照中未检测到。所有伴有HER 2 CNG的PC病例均表现出HER 2过表达,表明HER 2 CNG可能导致HER 2过表达。这些发现提供了新的见解犬PC的分子发病机制,这些可能是治疗相关的。患有PC的狗将可用作临床前大型动物模型,用于开发人类HER 2过表达前列腺癌的新疗法。
Human epidermal growth factor receptor 2 (HER2) is a cell surface receptor tyrosine kinase that belongs to the HER family. HER2 overexpression in human prostate cancer has been frequently observed; however, there are no reports on HER2 expression in canine prostate carcinoma (PC). The purpose of this study was to investigate HER2 expression and the underlying molecular mechanisms in canine PC. Twenty-one formalin-fixed paraffinembedded canine prostate gland tissues (13 carcinomas and 8 normal controls) were analyzed for HER2 expression using immunohistochemistry. Using a digital polymerase chain reaction assay, the HER2 copy number in 8 PC and 6 normal prostate gland tissues was determined. HER2 overexpression occurred in 8/13 (61.5%) PC cases, but not in the normal controls. There were no significant associations between HER2 overexpression and clinical characteristics of the PC cases, such as age, neuter status, lymph node involvement, distant metastasis, and overall survival. HER2 copy number gain (CNG) was detected in 3/8 (37.5%) PC cases, but not in the normal controls. All PC cases with HER2 CNG exhibited HER2 overexpression, suggesting that HER2 CNG may lead to HER2 overexpression. These findings provide new insights into the molecular pathogenesis of canine PC; these may be therapeutically relevant. Dogs with PC would be useful as a preclinical large animal model for the development of new therapy for HER2overexpressing prostate cancer in humans.