Immunohistochemical Localization of P‐Glycoprotein and Expression of the Multidrug Resistance‐1 Gene in Human Pancreatic Cancer: Relevance to Indicator of Better Prognosis

We investigated immunohistochemical localization of P‐glycoprotein (F‐gp) on paraffin‐embedded sections from 103 cases of previously untreated pancreatic tumors and also analyzed multidrug resistance‐1 (MDR1) gene expression by polymerase chain reaction after reverse transcription in 35 cases. High positive staining for P‐gp was observed in 72.8% of pancreatic tumors and in 73.2% of ductal adenocarcinoma. In ductal adenocarcinoma, immunoreactivity of P‐gp was inversely correlated with biological aggressiveness of tumors determined by histologic grading (P<0.01), tumor size (P<0.01), retroperitoneal invasion (P<0.01) and portal invasion (P<0.05). Expression of the MDR1 gene was detected in all the pancreatic tumors examined and was significantly higher than that in normal pancreas (P<0.05). The levels of MDR1 mRNA showed a moderate correlation with those of P‐gp (r=0.62, P<0.0001). Higher expression levels of MDR1/P‐gp significantly correlated with better prognosis of patients with ductal carcinoma (P<0.05). Among patients with ductal carcinoma, the high staining group for P‐gp revealed a 3.5‐fold better prognosis compared with the low staining group (HR=3.47, 95% CI=1.62, 7.45; P=0.0016). In conclusion, MDR1 gene/P‐gp expression in pancreatic cancer without chemotherapy inversely correlates with biological aggressiveness and is an independent indicator of favorable prognosis.