Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material
Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material
复制标题
DOI：
10.1002/path.1203
复制
发表时间：
2002-10-01
影响因子：
7.3
通讯作者：
Izquierdo, MA
中科院分区：
文献类型：
--
作者：
Diestra, JE;Scheffer, GL;Izquierdo, MA
乳腺癌耐药蛋白（BCPP/MXR/ABCP/ABCG2，以下简称ABCG2）是atp结合盒转运蛋白家族的一员，可引起对多种抗癌药物的多药耐药。ABCG2在人类肿瘤中的表达及其在临床耐药中的潜在作用尚不清楚。最近制备了两种抗人ABCG2的单克隆抗体，bmp -34和bmp -21。本研究描述了使用BXP-21免疫组织化学方法研究ABCG2在福尔马林固定石蜡包埋组织中的表达。使用相同方案的bmp -34未见染色。然后在包括21种肿瘤类型的150个未经治疗的人类实体肿瘤中研究ABCG2的表达。总体而言，ABCG2表达频繁。免疫组织化学特异性通过western blotting检测72kd条带证实。ABCG2在所有肿瘤类型中均有表达，但在消化道腺癌、子宫内膜腺癌、肺腺癌和黑色素瘤中似乎更为常见。阳性肿瘤呈膜质和细胞质染色。在某些腺癌中，可见明显的膜性染色。内皮细胞常显示中度至重度染色。ABCG2广泛存在于未经治疗的人类实体肿瘤中，可能代表了临床相关的耐药机制。需要对特定肿瘤类型进行进一步研究以确定其临床相关性。BXP-21和这里描述的免疫组织化学方案将在这些研究中有价值。版权所有:John Wiley Sons, Ltd。
Breast cancer resistance protein (BCPP/MXR/ABCP/ABCG2; hereafter ABCG2) is a member of the ATP-binding-cassette family of transporters that causes multi-drug resistance to various anticancer drugs. The expression of ABCG2 in human tumours and its potential involvement in clinical drug resistance are unknown. Recently, two monoclonal antibodies against human ABCG2 were produced, BXP-34 and BXP-21. This study describes an immunohistochemical method using BXP-21 to study ABCG2 expression in formalin-fixed, paraffin-embedded tissues. No staining was seen using BXP-34 with the same protocols. The expression of ABCG2 was then investigated in a panel of 150 untreated human solid tumours comprising 21 tumour types. Overall, ABCG2 expression was frequent. Specificity of immunohistochemistry was confirmed by the detection of a 72 kD band in western blotting. ABCG2 expression was seen in all tumour types, but it seemed more frequent in adenocarcinomas of the digestive tract, endometrium, and lung, and melanoma. Positive tumours showed membranous and cytoplasmic staining. In certain adenocarcinomas, prominent membranous staining was seen. Endothelial cells frequently displayed moderate to strong staining. ABCG2 is widely present in untreated human solid tumours and may represent a clinically relevant mechanism of drug resistance. Future studies in specific tumour types are needed to ascertain its clinical relevance. BXP-21 and the immunohistochemical protocol described here will be of value in these investigations. Copyright (C) 2002 John Wiley Sons, Ltd.