Detection of human epidermal growth factor receptor 2 overexpression in canine anal sac gland carcinoma
Detection of human epidermal growth factor receptor 2 overexpression in canine anal sac gland carcinoma
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DOI：
10.1292/jvms.19-0019
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发表时间：
2019-07-01
影响因子：
1.2
通讯作者：
Nakagawa, Takayuki
中科院分区：
文献类型：
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作者：
Yoshimoto, Sho;Kato, Daiki;Nakagawa, Takayuki
犬肛囊腺癌（ASGC）好发于犬肛囊顶泌腺，具有侵袭性生物学行为。人表皮生长因子受体2（HER 2）的表达已被报道在各种人类和犬肿瘤。HER 2是这些肿瘤的一个有前途的治疗靶点，靶向HER 2的药物，如曲妥珠单抗和拉帕替尼，已经改善了这些患者的预后。在这项研究中，评估了HER 2在ASGC中的表达，以研究其作为犬ASGC治疗靶点的潜力。手术切除的ASGC组织中HER 2 mRNA的表达显著高于正常肛囊组织。为了评价HER 2蛋白的表达，对石蜡包埋的ASGC组织进行了化学染色评价。在ASGC组织中检测到强烈和广泛的HER 2染色，而HER 2在正常肛囊顶泌腺和鳞状上皮中弱至中度染色。根据其强度和阳性程度对ASGC组织中HER 2表达的程度进行评分（评分：0-3+）。HER 2表达评分显示6份样本（24%）评分为3+，14份样本（56%）评分为2+，5份样本（20%）评分为1+，无样本评分为0。总之，80%的犬ASGC组织为HER 2阳性（评分>= 2+）。此外，通过流式细胞术用曲妥珠单抗检测ASGC中推定的HER 2过表达细胞。这些初步数据可能会进一步评估HER 2在犬ASGC中作为恶性肿瘤机制和HER 2靶向治疗的治疗靶点的作用。
Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the outcome of these patients. In this study, HER2 expression in ASGC was evaluated to investigate its potential as a therapeutic target for canine ASGC. HER2 mRNA expression in surgically resected ASGC tissues was significantly higher than that in normal anal sac tissue. To evaluate the expression of HER2 protein, paraffin-embedded ASGC tissues were immunohistochemically evaluated. Strong and broad staining of HER2 was detected in ASGC tissues, while HER2 was weakly to moderately stained in normal anal sac apocrine glands and squamous epithelia. The degree of HER2 expression in ASGC tissues was scored based on its intensity and positivity (score: 0-3+). Scoring of HER2 expression revealed 6 samples (24%) scored 3+, 14 (56%) scored 2+, and 5 (20%) scored 1+, with no samples scoring 0. In all, 80% of canine ASGC tissues were positive for HER2 (scored >= 2+). Furthermore, putative HER2-overexpressed cells in ASGC were detected with trastuzumab by flow cytometry. These preliminary data may lead to further evaluation of the role of HER2 in canine ASGC as a mechanism of malignancy and as a therapeutic target for HER2-targeted therapy.