Cao L, Duchrow M, Windhövel U, Kujath P, Bruch H P, Broll R
Surgical Research, Medical University of Lübeck, Germany.
Eur J Cancer. 1998 Sep;34(10):1612-7. doi: 10.1016/s0959-8049(98)00142-7.
The aim of this study was to examine the expression of P-glycoprotein (Pgp) and MDR1 mRNA, in gall bladder carcinoma, a chemo-resistant tumour. 26 cases of gall bladder cancer and nine samples of normal gall bladder archival paraffin blocks were investigated for the presence of Pgp protein with immunohistochemistry (IHC) and MDR1 RNA by reverse transcription-polymerase chain reaction (RT-PCR). Monoclonal antibodies JSB-1 and UIC-2, recognising separate epitopes of Pgp, were used for IHC. For RT-PCR, total RNA was extracted from paraffin-embedded tissue. After RT, the samples were subjected to nested PCR (NPCR) using primers specific for the MDR1 gene, and evaluated by electrophoresis. In gall bladder carcinoma, the percentage of positive cases expressing Pgp (77% for JSB-1, 69% for UIC-2) and MDR1 mRNA (52%) was significantly higher than those in normal gall bladder. In earlier TNM stages Pgp and MDR1 mRNA were more frequently expressed (non-significant) than in advanced stages. The results of this study suggested that overexpression of MDR1 mRNA and Pgp in gall bladder carcinoma tissue probably is a very important reason why gall bladder cancer is generally not responsive to chemotherapy.
本研究旨在检测胆囊癌（一种化疗耐药肿瘤）中P-糖蛋白（Pgp）和多药耐药基因1（MDR1）mRNA的表达情况。采用免疫组织化学（IHC）法检测26例胆囊癌及9例正常胆囊存档石蜡块中Pgp蛋白的表达，采用逆转录聚合酶链反应（RT-PCR）检测MDR1 RNA的表达。免疫组织化学使用识别Pgp不同表位的单克隆抗体JSB-1和UIC-2。逆转录聚合酶链反应中，从石蜡包埋组织中提取总RNA。逆转录后，样品使用针对MDR1基因的引物进行巢式PCR（NPCR），并通过电泳进行评估。在胆囊癌中，表达Pgp（JSB-1为77%，UIC-2为69%）和MDR1 mRNA（52%）的阳性病例百分比显著高于正常胆囊。在较早的TNM分期中，Pgp和MDR1 mRNA的表达频率（无显著性差异）高于晚期。本研究结果提示，胆囊癌组织中MDR1 mRNA和Pgp的过表达可能是胆囊癌通常对化疗无反应的一个非常重要的原因。
