Expression And Significance Of ABCG2 And P-gp In Pancreatic Cancer

IntroductionPancreatic cancer has the worst prognosis.Multidrug resistance and tumor stem cells is related to the worst prognosis. the SP phenotype of tumor stem cells is related to the ABCG2, ABCG2 and P-gp both belong to the ATP binding cassette transporter protein super-family. P-gp is a classic multidrug resistance protein,there have been mang research about it. Since ABCG2 and P-gp have the similar function in pharmacology, the same distribution in normal tissues and organs, and their expression are all related to tumor micro-environment,such as hypoxia etc. Our research will be done to study relation among these proteins in pancreatic cancer and the clinical characteristics in order to speculate whether two proteins have the same expression and regulation of approach.In this study, immunohistochemical SP method was used to detected ABCG2 and P-gp expression in pancreatic cancer cells, and statistical methods were used to test whether ABCG2 and P-gp expression in pancreatic cancer have ang relationship with tumor size, pathologic stage, histological differentiation and lymph node metastasis in clinicopathologic factors.Methods1.PatientsSelect resection paraffin tissue of pancreatic cancer and duodenal cancer (no violation of pancreas) as normal pancreatic from Shengjing China Medical University Hospital Department of General Surgery in 2006-2009. All specimens have detailed clinical information, and in primary cases did not receive preoperative radiotherapy, chemotherapy and other anti-cancer therapy.67 cases in pancreatic cancer group, the normal surgical resection of the pancreas are 12 cases.2. Materials The monoclonal antibodies against ABCG2 purchased from american santa Inc; The monoclonal antibodies against P-gp and SP immunohistochemical kits and were purchased from Fujian Maixin Biotechology, Inc; DAB substrate solution were purchased from Beijing Zhongshan Golden Bridge Biotechnology Inc.3.MethodsImmunohistochemical staining SP method was performed. All slides were treated with 0.01 mol/L ethylene diamine tetraacetic acid buffer (PH=9.0) and recovered the antigen activity by autoclave.4. AssessmentOutcome definition of ABCG2 and P-gp were stained palm yellow particle in cell membrane and Cytoplasm, positive cells≤5% as negative,>5% as positive, at high magnification(400 X).5. Statistical analysisStatistical methods X2 test and Spearman rank correlation test were performed by SPSS software version 17.0.Result1.ABCG2 protein expresses in the tumor cell membrane and cytoplasm, no nucleus membrane expression. ABCG2-positive 42 cases (62.7%), negative 25 cases (37.3%). P-gp expresses at the membrane and cytoplasm of tumor cells. P-gp positive in 54 (80.6%). P-gp negative expression in 13 cases (19.4%). ABCG2 and P-gp in 12 cases of normal pancreas were negative.2.ABCG2 and tumor size (r= 0.305, p= 0.012) were positive correlated, negative correlated with tumor differentiation (r=-0.325, p= 0.014), and there was弄significantly correlated with the clinical stage and lymph node metastasis. P-gp was no correlated with clinical stage of tumor differentiation, tumor size and lymph node metastasis etc. (P> 0.05)3.ABCG2 and p-gp have positive correlation by statistical analysis r= 0.246, P 0.045<0.05.Conclusion1. ABCG2 positive cells in pancreatic cancer stem cell research can be considered in the SP cells, suggest a higher tendency of recurrence and metastasis. 2. ABCG2 positive results with pancreatic tumor specimens larger poorer differen-tiation were higher. ABCG2-positive or P-gp-positive in clinical use guide to select sensitive chemotherapy drugs and the treatment which aim at two kinds of protein has instruction meaning3. Pancreatic expression of ABCG2 and P-gp positive correlation may exist between the expression of mutual inhibition, the same regulatory pathway may exist and the adjustment in the same direction.