Wright S R, Boag A H, Valdimarsson G, Hipfner D R, Campling B G, Cole S P, Deeley R G
Department of Pathology, Queen's University, Kingston, Ontario, Canada.
Clin Cancer Res. 1998 Sep;4(9):2279-89.
Monoclonal antibody QCRL-1 is highly specific for a defined linear epitope in a relatively poorly conserved region of the human multidrug resistance protein (MRP). We have used QCRL-1 to examine MRP expression in archival and fresh snap-frozen samples of untreated small cell (SC) and non-small cell (NSC) lung cancers (LCs), as well as normal lung. We found that the majority (87%) of all histological subtypes of NSCLC had detectable levels of MRP in most of the tumor mass. In a substantial proportion of adenocarcinomas (55%) and squamous cell carcinomas (28%), immunoreactivity approached that obtained with the highly multidrug resistant cell line H69AR from which the MRP was originally cloned. Both the level and frequency of MRP expression in untreated SCLC was significantly lower than in NSCLC. The MRP was detectable in only 56% of SCLC tumors and, in most cases, was expressed in small focal clusters of cells. Immunofluorescence studies of tumor tissue and normal lung confirmed the plasma membrane location of the MRP. However, in normal bronchial epithelium and seromucous glands, unlike in tumor cells, the MRP was detected only on basolateral membranes. In addition, strong MRP immunoreactivity was detected in reactive type II pneumocytes present in hyperplastic alveoli, but not in normal type I and type II pneumocytes. No potentially confounding correlation independent of its possible role in drug resistance was observed between MRP expression in untreated NSCLC and any clinicopathological parameter examined, including overall survival.
单克隆抗体QCRL-1对人多药耐药蛋白（MRP）相对保守性较差区域中的特定线性表位具有高度特异性。我们使用QCRL-1检测了未经治疗的小细胞（SC）和非小细胞（NSC）肺癌（LC）存档及新鲜速冻样本以及正常肺组织中的MRP表达。我们发现，非小细胞肺癌所有组织学亚型中的大多数（87%）在大部分肿瘤组织中都有可检测到的MRP水平。在相当比例的腺癌（55%）和鳞状细胞癌（28%）中，免疫反应性接近最初克隆MRP的高度多药耐药细胞系H69AR的水平。未经治疗的小细胞肺癌中MRP表达的水平和频率均显著低于非小细胞肺癌。仅56%的小细胞肺癌肿瘤中可检测到MRP，且在大多数情况下，其在小灶性细胞簇中表达。肿瘤组织和正常肺组织的免疫荧光研究证实了MRP定位于质膜。然而，在正常支气管上皮和浆液黏液腺中，与肿瘤细胞不同，MRP仅在基底外侧膜上被检测到。此外，在增生性肺泡中存在的反应性II型肺泡上皮细胞中检测到强MRP免疫反应性，但在正常I型和II型肺泡上皮细胞中未检测到。在未经治疗的非小细胞肺癌中，未观察到MRP表达与所检测的任何临床病理参数（包括总生存期）之间存在与其在耐药性中可能作用无关的潜在混杂相关性。
