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犬淋巴瘤中P糖蛋白(多药耐药蛋白1)免疫组织化学的评估——预后及临床方面

Evaluation of Pgp (MDR1) immunohistochemistry in canine lymphoma - prognostic and clinical aspects.

作者信息

Vajdovich Péter, Koltai Zsófia, Dékay Valéria, Kungl Krisztina, Harnos Andrea

机构信息

1 Department of Clinical Pathology and Oncology University of Veterinary Medicine , István u. 2, H-1078 Budapest , Hungary.

2 Veterinary Haematology and Oncology Centre , Budapest , Hungary.

出版信息

Acta Vet Hung. 2018 Jun;66(2):309-328. doi: 10.1556/004.2018.028.

DOI:10.1556/004.2018.028
PMID:29958524
Abstract

Permeability glycoprotein (P-glycoprotein, Pgp) immunohistochemistry (IHC) was evaluated in dogs with multicentric lymphoma treated with cyclophosphamide- doxorubicin-vincristine-prednisolone with or without L-Asparaginase. Lymph nodes of 33 untreated dogs were immunophenotyped: Ki67% and Pgp analyses (with anti-Pgp, monoclonal mouse C494 clone) were performed. Pgp positivity rate and intensity were determined microscopically (by manual counting done by two blinded authors in two parallel specimens). The median overall survival time (OST) was 333 days and the relapse-free period (RFP) 134 days. Pgp expressions were positive in 18 out of 33 (54.5%) of tumour cells. T-cell types stained more intensively. Lower OST and RFP were found with Pgp positivity ≥ 35% (OST: 240 days, RFP: 95 days) compared to Pgp positivity < 35% (OST: 428 days, RFP: 232 days). Intensive staining was associated with a lower OST and RFP (240 and 103 days, respectively) than weak staining (428 and 221 days, respectively). Death due to adverse drug reactions was best predicted at Pgp positivity ≤ 6.5% (sensitivity/specificity: 0.55/0.81) and ≤ 123 days (sensitivity/ specificity: 0.55/0.86). Pgp evaluation by IHC can have prognostic value with a properly established Pgp% positivity cut-off value in dogs treated with Pgp substrate drugs.

摘要

对接受环磷酰胺-阿霉素-长春新碱-泼尼松龙治疗(联合或不联合L-天冬酰胺酶)的多中心淋巴瘤犬进行了通透性糖蛋白(P-糖蛋白,Pgp)免疫组化(IHC)评估。对33只未经治疗的犬的淋巴结进行免疫表型分析:进行Ki67%和Pgp分析(使用抗Pgp单克隆小鼠C494克隆)。通过显微镜(由两名不知情的作者在两个平行样本中进行手动计数)确定Pgp阳性率和强度。中位总生存时间(OST)为333天,无复发生存期(RFP)为134天。33个肿瘤细胞中有18个(54.5%)Pgp表达呈阳性。T细胞类型染色更强烈。与Pgp阳性率<35%(OST:428天,RFP:232天)相比,Pgp阳性率≥35%时(OST:240天,RFP:95天)的OST和RFP更低。与弱阳性(分别为428天和221天)相比,强染色与更低的OST和RFP(分别为240天和103天)相关。当Pgp阳性率≤6.5%(敏感性/特异性:0.55/0.81)和≤123天(敏感性/特异性:0.55/0.86)时,药物不良反应导致的死亡预测效果最佳。在使用Pgp底物药物治疗的犬中,通过IHC评估Pgp并适当确定Pgp%阳性临界值可能具有预后价值。

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