Immunohistochemical Analysis of Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 and Enolase 1 in Canine Mammary Tumors: Associations with Tumor Aggressiveness and Prognostic Significance.

IF 2 2区 农林科学 Q2 VETERINARY SCIENCES
Luadna Dos Santos E Silva, Pedro Henrique Fogaça Jordão, Beatriz Castilho Balieiro, Laura de Souza Baracioli, Daniela Farias de Nóbrega, Adriana Alonso Novais, Luiz Gustavo de Almeida Chuffa, Debora Aparecida Pires de Campos Zuccari
{"title":"Immunohistochemical Analysis of Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 and Enolase 1 in Canine Mammary Tumors: Associations with Tumor Aggressiveness and Prognostic Significance.","authors":"Luadna Dos Santos E Silva, Pedro Henrique Fogaça Jordão, Beatriz Castilho Balieiro, Laura de Souza Baracioli, Daniela Farias de Nóbrega, Adriana Alonso Novais, Luiz Gustavo de Almeida Chuffa, Debora Aparecida Pires de Campos Zuccari","doi":"10.3390/vetsci12020110","DOIUrl":null,"url":null,"abstract":"<p><p>Mammary neoplasms in dogs are a common clinical concern, especially in middle-aged and older intact females. These tumors share similarities with human breast cancer in terms of histology, disease progression, and risk factors, making dogs a relevant model for breast cancer research. The search for biomarkers in canine mammary tumors is essential to understand tumor progression and identify potential therapeutic targets. This study investigated the expression of two potential biomarkers-Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 (ITIH2) and Enolase 1 (ENO1)-in the mammary glands of healthy and tumor-bearing dogs using immunohistochemistry. Both proteins were identified in previous proteomic analyses of extracellular vesicles derived from the plasma of healthy and tumor-bearing dogs. A total of fifty-one canine mammary tissue samples were analyzed and categorized into three groups: (i) the control group, composed of five samples of normal mammary tissue without neoplasia; (ii) benign tumors, composed of nineteen samples of benign mixed tumors; and (iii) malignant tumors, which included six carcinomas in grade 1 mixed tumors, five carcinomas in grade 2 mixed tumors, thirteen solid carcinomas of grade 3, one papillary carcinoma, and two tubular carcinomas. Regarding the intensity of staining, quantified by histoscore, there were no significant differences in the comparison between the groups; for ITIH2, the <i>p</i>-value was 0.33, and for ENO1, the <i>p</i>-value was 0.57. Regarding the predictive potential of their respective ROC curves, the proteins demonstrated low predictive power in canine mammary tumors. These findings indicate that neither ITIH2 nor ENO1 demonstrated strong prognostic value in this setting, as demonstrated by their moderate AUC values, wide confidence intervals, and lack of statistical significance. However, this study found distinct tissue localization patterns for ITIH2 and subcellular localization for ENO1. As an additional way to examine possible associations of these proteins with epithelial-mesenchymal transition, the ZEB1 antibody was tested by both single and double immunohistochemistry, demonstrating a tendency to be more intensely expressed in the malignant group and tending to be associated with ENO1 in canine mammary tumors.</p>","PeriodicalId":23694,"journal":{"name":"Veterinary Sciences","volume":"12 2","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860171/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary Sciences","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.3390/vetsci12020110","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Mammary neoplasms in dogs are a common clinical concern, especially in middle-aged and older intact females. These tumors share similarities with human breast cancer in terms of histology, disease progression, and risk factors, making dogs a relevant model for breast cancer research. The search for biomarkers in canine mammary tumors is essential to understand tumor progression and identify potential therapeutic targets. This study investigated the expression of two potential biomarkers-Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 (ITIH2) and Enolase 1 (ENO1)-in the mammary glands of healthy and tumor-bearing dogs using immunohistochemistry. Both proteins were identified in previous proteomic analyses of extracellular vesicles derived from the plasma of healthy and tumor-bearing dogs. A total of fifty-one canine mammary tissue samples were analyzed and categorized into three groups: (i) the control group, composed of five samples of normal mammary tissue without neoplasia; (ii) benign tumors, composed of nineteen samples of benign mixed tumors; and (iii) malignant tumors, which included six carcinomas in grade 1 mixed tumors, five carcinomas in grade 2 mixed tumors, thirteen solid carcinomas of grade 3, one papillary carcinoma, and two tubular carcinomas. Regarding the intensity of staining, quantified by histoscore, there were no significant differences in the comparison between the groups; for ITIH2, the p-value was 0.33, and for ENO1, the p-value was 0.57. Regarding the predictive potential of their respective ROC curves, the proteins demonstrated low predictive power in canine mammary tumors. These findings indicate that neither ITIH2 nor ENO1 demonstrated strong prognostic value in this setting, as demonstrated by their moderate AUC values, wide confidence intervals, and lack of statistical significance. However, this study found distinct tissue localization patterns for ITIH2 and subcellular localization for ENO1. As an additional way to examine possible associations of these proteins with epithelial-mesenchymal transition, the ZEB1 antibody was tested by both single and double immunohistochemistry, demonstrating a tendency to be more intensely expressed in the malignant group and tending to be associated with ENO1 in canine mammary tumors.

犬乳腺肿瘤中α -胰蛋白酶抑制剂重链2和烯醇化酶1的免疫组织化学分析:与肿瘤侵袭性和预后意义的关系
狗的乳腺肿瘤是一种常见的临床问题,特别是在中年和老年完整的雌性中。这些肿瘤在组织学、疾病进展和危险因素方面与人类乳腺癌有相似之处,使狗成为乳腺癌研究的相关模型。在犬乳腺肿瘤中寻找生物标志物对于了解肿瘤进展和确定潜在的治疗靶点至关重要。本研究利用免疫组织化学方法研究了两种潜在的生物标志物- α -胰蛋白酶抑制剂重链2 (ITIH2)和烯醇化酶1 (ENO1)在健康和荷瘤犬乳腺中的表达。这两种蛋白都是在之前对健康犬和患瘤犬的血浆细胞外囊泡进行的蛋白质组学分析中鉴定出来的。对51份犬乳腺组织样本进行分析,并将其分为三组:(i)对照组,由5份未发生瘤变的正常乳腺组织样本组成;(ii)良性肿瘤,由19例良性混合肿瘤组成;(iii)恶性肿瘤,包括6例1级混合瘤,5例2级混合瘤,13例3级实体癌,1例乳头状癌,2例管状癌。通过histoscore量化染色强度,各组间比较无显著差异;ITIH2的p值为0.33,ENO1的p值为0.57。关于其各自ROC曲线的预测潜力,蛋白质在犬乳腺肿瘤中的预测能力较低。这些发现表明,ITIH2和ENO1在这种情况下都没有很强的预后价值,因为它们的AUC值适中,置信区间宽,缺乏统计学意义。然而,本研究发现ITIH2的组织定位模式不同,而ENO1的亚细胞定位模式不同。作为检验这些蛋白与上皮-间质转化可能关联的另一种方法,ZEB1抗体通过单免疫组织化学和双免疫组织化学测试,显示在恶性组中表达更强烈,并且倾向于与犬乳腺肿瘤中的ENO1相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Veterinary Sciences
Veterinary Sciences VETERINARY SCIENCES-
CiteScore
2.90
自引率
8.30%
发文量
612
审稿时长
6 weeks
期刊介绍: Veterinary Sciences is an international and interdisciplinary scholarly open access journal. It publishes original that are relevant to any field of veterinary sciences, including prevention, diagnosis and treatment of disease, disorder and injury in animals. This journal covers almost all topics related to animal health and veterinary medicine. Research fields of interest include but are not limited to: anaesthesiology anatomy bacteriology biochemistry cardiology dentistry dermatology embryology endocrinology epidemiology genetics histology immunology microbiology molecular biology mycology neurobiology oncology ophthalmology parasitology pathology pharmacology physiology radiology surgery theriogenology toxicology virology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信