Immunohistochemical detection of P-glycoprotein in formalin-fixed and paraffin-embedded normal and neoplastic canine tissues
Immunohistochemical detection of P-glycoprotein in formalin-fixed and paraffin-embedded normal and neoplastic canine tissues
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DOI：
10.1177/030098589603300508
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发表时间：
1996-09-01
影响因子：
2.4
通讯作者：
Ginn, PE
中科院分区：
文献类型：
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作者：
Ginn, PE
p -糖蛋白是一种系统发育保守的整体质膜蛋白，其表达是肿瘤细胞多药耐药的重要因素之一。采用三种针对p -糖蛋白分子不同表位的小鼠单克隆抗体（C494, C219, JSB-1），采用亲和素-生物素复合物技术对福尔马林固定、石蜡包埋的正常和肿瘤犬组织进行了研究。正常犬组织的免疫染色结果显示，在肝脏、近端肾小管上皮、肾上腺皮质、结肠上皮和脑毛细血管内皮细胞中，每种抗体都检测到阳性标记。对166例上皮或间充质来源的肿瘤进行p -糖蛋白免疫反应性评估。肝癌（4/4）、结直肠腺瘤（7/7）、结直肠癌（4/4）、肾上腺皮质腺瘤（3/3）、血管外皮细胞瘤（15/15）、大汗腺腺癌（4/5,80%）和移行细胞癌（2/2）一致标记有至少一种抗体。组织细胞瘤（0/10）、皮肤浆细胞瘤（0/10）、纤维瘤（0/3）、纤维肉瘤（0/4）和平滑肌瘤（0/4）的所有抗体均为阴性。恶性淋巴瘤（6/22,27.3%）、恶性黑色素瘤（4/13,30.8%）、平滑肌肉瘤（3/6,50%）、乳腺癌（12/19,63.2%）、乳腺腺瘤（3/9,33.3%）、鳞状细胞癌（8/10,80%）、基底细胞瘤（5/7,71.4%）、大汗腺腺瘤（1/2,50%）、胆管癌（2/3,66.7%）和甲状腺癌（2/4,50%）的结果各不相同。抗体C494、JSB-1和C219分别标记了所有肿瘤的66/166（39.8%）、53/166（31.9%）和38/166（22.9%）。共有26/166（15.7%）、22/166（13.3%）和37/166（22.6%）的肿瘤分别被三种抗体、两种抗体和一种抗体单独标记。抗体C494是唯一标记28/166（16.9%）的抗体。JSB-1单独标记9/166（5.4%）的肿瘤。C219不能标记任何未被C494或JSB-1标记的肿瘤。C494的标记比其他两种抗体的标记更强烈和特异性。结果表明，p -糖蛋白可在常规处理犬组织中检测到。p -糖蛋白在犬肝、肾、肾上腺和结肠以及这些组织产生的肿瘤中的检测结果与文献中对人体组织的报道一致。其他肿瘤如恶性淋巴瘤和乳腺癌的可变标记结果也与人类研究报告一致。犬类组织中p -糖蛋白等多药耐药标记物的检测可以为犬类肿瘤的预后或治疗方案的设计提供额外的信息。
Expression of P-glycoprotein, a phylogenetically conserved integral plasma membrane protein, is implicated as one of the most important factors contributing to tumor cell multidrug resistance. Formalin-fixed, paraffin-embedded normal and neoplastic canine tissues were studied using an avidin-biotin complex technique employing three murine monoclonal antibodies (C494, C219, JSB-1) to different epitopes of the P-glycoprotein molecule. Evaluation of immunostaining of normal canine tissues revealed positive labeling detected by each antibody in the liver, proximal renal tubular epithelium, adrenal cortex, colonic epithelium, and capillary endothelial cells of the brain. A total of 166 tumors of epithelial or mesenchymal origin were evaluated for P-glycoprotein immunoreactivity. Hepatomas (4/4), colorectal adenomas (7/7), colorectal carcinomas (4/4), adrenal cortical adenomas (3/3), hemangiopericytomas (15/15), apocrine gland adenocarcinomas (4/5, 80%), and transitional cell carcinomas (2/2) consistently labeled with at least one of the antibodies. Histiocytomas (0/10), cutaneous plasma cell tumors (0/10), fibromas (0/3), fibrosarcomas (0/4), and leiomyomas (0/4) were uniformly negative with all antibodies. Malignant lymphomas (6/22, 27.3%), malignant melanomas (4/13, 30.8%), leiomyosarcomas (3/6, 50%), mammary gland carcinomas (12/19, 63.2%), mammary gland adenomas (3/9, 33.3%), squamous cell carcinomas (8/10, 80%), basal cell tumors (5/7, 71.4%), apocrine gland adenomas (1/2, 50%), cholangiocarcinomas (2/3, 66.7%), and thyroid gland carcinomas (2/4, 50%) gave variable results. The antibodies C494, JSB-1, and C219 labeled 66/166 (39.8%), 53/166 (31.9%), and 38/166 (22.9%) of all tumors studied, respectively. A total of 26/166 (15.7%), 22/166 (13.3%), and 37/166 (22.6%) of tumors were labeled by all three, just two, or one antibody alone, respectively. The antibody C494 was the only antibody labeling 28/166 (16.9%) of the cases. JSB-1 alone labeled 9/166 (5.4%) of the tumors. C219 failed to label any tumors not also labeled by either C494 or JSB-1. Labeling by C494 was more intense and specific than labeling by the other two antibodies. Results indicate that P-glycoprotein can be detected in routinely processed canine tissues. The detection of P-glycoprotein within canine liver, kidney, adrenal gland, and colon and within tumors arising from these tissues is consistent with that reported in the literature for human tissues. Variable labeling results of other tumors such as malignant lymphoma and mammary gland carcinomas also is consistent with reports of human studies. Detection of multidrug resistance markers such as P-glycoprotein in canine tissues may provide additional information upon which to base a prognosis or to design treatment regimens for canine tumors.