Expression of the Multidrug-Resistance 1 (MDR1) Gene and Prognosis in Human Pancreatic Cancer

作者：Lu Zhao, Jörg Kleeff, Shailesh V. Shrikhande, Arthur Zimmermann, Murray Korc, Helmut Friess, Markus W. B chler · 发表于：Pancreas · 年份：2000 · DOI：10.1097/00006676-200010000-00004 · 被引用次数：52 · 研究领域：Drug Transport and Resistance Mechanisms、Pancreatic and Hepatic Oncology Research、Cholangiocarcinoma and Gallbladder Cancer Studies

Multidrug-resistance 1 (MDR1) encodes a 170 kDa transmembrane glycoprotein (P-glycoprotein), which acts as a drug-efflux pump. In the present study, we analyzed the expression of MDR1/P-glycoprotein in human pancreatic cancer and correlated the results with clinical parameters. Pancreatic cancer tissue samples were obtained from 67 patients (30 female, 37 male) who underwent surgery. Normal pancreatic tissues obtained from 15 previously healthy organ donors (4 female, 11 male) served as controls. MDR1 mRNA levels were analyzed by Northern blotting, and the exact site of MDR1 mRNA expression was determined by in situ hybridization and immunohistochemistry. Northern blot analysis indicated that in comparison with the normal pancreas, MDR1 mRNA levels were only increased 1.4-fold (p = 0.03) in the pancreatic cancer samples. However, there was a 2.9-fold (p < 0.01) increase in MDR1 mRNA levels when only the samples that exhibited increased expression (38%) were analyzed. In situ hybridization and immunohistochemical analysis showed that MDR1 was highly expressed in the cancer cells of these samples. Statistical analysis revealed that patients with high MDR1/P-glycoprotein expression had a shorter postoperative survival time compared with patients with weak to moderate expression of MDR1. On the basis of in situ hybridization, survival in the intense group was 11.6 (n = 12) versus 14.2 months (n = 42) in the mild to moderate group. On the basis of immunohistochemistry, survival in...