Sakai Kosei, Chambers James Ken, Uchida Kazuyuki, Nakagawa Takayuki, Nishimura Ryohei, Yonezawa Tomohiro, Maeda Shingo
Department of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
J Vet Med Sci. 2021 Mar 11;83(3):370-377. doi: 10.1292/jvms.20-0483. Epub 2021 Jan 19.
Copy number gain (CNG) and/or protein overexpression of ErbB2 have been observed in human breast cancer patients and are associated with poor prognosis. Similarly, ErbB2 overexpression has also been observed in canine mammary carcinoma; however, data on ErbB2 copy number is limited. The purposes of this study were to evaluate ErbB2 copy number in dogs with mammary carcinoma and to investigate associations of ErbB2 CNG with ErbB2 expression, histological and clinical characteristics, and survival. DNA samples were isolated from 59 formalin-fixed paraffin-embedded canine mammary gland tissues (34 carcinoma, 14 adenoma, and 11 normal). Using a digital PCR assay, the ErbB2 copy number in these samples was determined as compared to a reference gene on canine chromosome 8. ErbB2 CNG was detected in 14/34 (41%) carcinomas and 2/14 (14%) adenomas. ErbB2 overexpression was observed in 3/34 (9%) carcinomas but not in adenomas. Neither ErbB2 CNG nor ErbB2 overexpression were detected in the normal controls. There was no significant association of the ErbB2 CNG with histological and clinical characteristics such as age, neutered status, histological grade, tumor size, lymph node involvement, distant metastasis, and clinical stage in the dogs with mammary carcinoma. The presence of ErbB2 CNG, but not ErbB2 overexpression, was significantly related to the shorter overall survival. These findings suggest that ErbB2 CNG is a prognostic factor in dogs with mammary carcinoma.
在人类乳腺癌患者中已观察到表皮生长因子受体2（ErbB2）的拷贝数增加（CNG）和/或蛋白过表达，且与预后不良相关。同样，在犬乳腺癌中也观察到了ErbB2过表达；然而，关于ErbB2拷贝数的数据有限。本研究的目的是评估患乳腺癌犬的ErbB2拷贝数，并研究ErbB2 CNG与ErbB2表达、组织学和临床特征以及生存情况之间的关联。从59份福尔马林固定石蜡包埋的犬乳腺组织（34份癌组织、14份腺瘤组织和11份正常组织）中分离出DNA样本。使用数字PCR检测法，将这些样本中的ErbB2拷贝数与犬8号染色体上的一个参考基因进行比较来确定。在14/34（41%）的癌组织和2/14（14%）的腺瘤组织中检测到ErbB2 CNG。在3/34（9%）的癌组织中观察到ErbB2过表达，但在腺瘤组织中未观察到。在正常对照中未检测到ErbB2 CNG和ErbB2过表达。在患乳腺癌的犬中，ErbB2 CNG与年龄、绝育状态、组织学分级、肿瘤大小、淋巴结受累情况、远处转移和临床分期等组织学和临床特征之间无显著关联。ErbB2 CNG的存在而非ErbB2过表达与较短的总生存期显著相关。这些发现表明ErbB2 CNG是患乳腺癌犬的一个预后因素。
