Itsubo M, Ishikawa T, Toda G, Tanaka M
First Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Cancer. 1994 Jan 15;73(2):298-303. doi: 10.1002/1097-0142(19940115)73:2<298::aid-cncr2820730211>3.0.co;2-4.
Expression and cellular localization of the multidrug resistance gene product P-glycoprotein, which plays an important role in multidrug resistance to cancer chemotherapy, were immunohistochemically studied in paraffin sections from 55 patients with primary liver carcinoma.
Tumor samples from 43 patients with hepatocellular carcinoma (HCC) and from 12 with cholangiocellular carcinoma (CCC) were obtained at autopsy or at surgical resection. Immunohistochemical study was performed by the avidin-biotin-peroxidase technique using monoclonal antibody JSB-1 directed against P-glycoprotein.
Anti-P-glycoprotein immunostaining was observed in 67.4% of cases with HCC and in 66.7% of cases with CCC. When P-glycoprotein was detected in HCC, it was localized on the contact surface among tumor cells regardless of histologic type and on the cellular surface facing the blood space in the trabecular type and on the luminal surface in the pseudoglandular type. In CCC, relatively weak immunoreactivity for P-glycoprotein was localized in the cytoplasm of tumor cell both in glandular and nonglandular types, and stronger immunoreactivity was sometimes seen on the luminal surface of glandular type. The incidence of expression of P-glycoprotein was not influenced by previous cancer chemotherapy both in HCC and CCC. In the trabecular type of HCC, however, all cases with P-glycoprotein expression on the cellular surface facing the blood space were from the patients treated with antitumor agents.
Resistance to cancer chemotherapy in primary liver carcinoma results from P-glycoprotein protein expression.
多药耐药基因产物P-糖蛋白在癌症化疗的多药耐药中起重要作用，对55例原发性肝癌石蜡切片进行免疫组织化学研究，观察其表达及细胞定位。
取自43例肝细胞癌（HCC）和12例胆管细胞癌（CCC）患者的肿瘤样本，于尸检或手术切除时获取。采用抗P-糖蛋白单克隆抗体JSB-1，通过抗生物素蛋白-生物素-过氧化物酶技术进行免疫组织化学研究。
HCC患者中67.4%的病例及CCC患者中66.7%的病例观察到抗P-糖蛋白免疫染色。在HCC中检测到P-糖蛋白时，无论组织学类型如何，其定位于肿瘤细胞之间的接触面，在小梁型中定位于面向血窦的细胞表面，在假腺管型中定位于管腔表面。在CCC中，P-糖蛋白相对较弱的免疫反应性定位于腺管型和非腺管型肿瘤细胞的细胞质中，在腺管型的管腔表面有时可见较强的免疫反应性。P-糖蛋白的表达发生率在HCC和CCC中均不受先前癌症化疗的影响。然而，在小梁型HCC中，所有在面向血窦的细胞表面表达P-糖蛋白的病例均来自接受过抗肿瘤药物治疗的患者。
原发性肝癌对癌症化疗的耐药性源于P-糖蛋白的蛋白表达。
