title: Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients.
abstract: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal even after complete resection, with most recurrences occurring within 1-2 years postoperatively. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been demonstrated to play major roles in multidrug resistance (MDR) of cancers. In this study, we evaluated the expression statuses and the clinical significance of MDR1 (ABCB1), MDR-associated proteins (MRPs/ABCC) 1, 2 and 3, and breast cancer resistance protein (BCRP/ABCG2) in 67 surgically resected PDACs by immunohistochemistry. MDR1, MRP1, MRP2, MRP3 and BCRP were expressed in 35 (52.2%), 56 (83.6%), 61 (91.0%), 49 (73.1%) and 49 (73.1%) out of 67 cases, respectively. The expression statuses of the MDR-related proteins were positively correlated with each other (P < 0.05). Tumors expressing MRP1 (P= 0.015), MRP2 (P= 0.022) and MRP3 (P < 0.001) demonstrated more frequent perineural invasion. MDR1 expression was significantly correlated with lymphatic invasion (P= 0.047). High BCRP expression in PDAC was a significant prognostic factor for early tumor recurrence (HR = 2.43, P= 0.003) and poor survival (HR = 2.63, P= 0.001). MDR-related proteins are frequently expressed in PDAC, and high BCRP expression is a significant independent predictor for early recurrence and poor survival. Immunohistochemical analysis for BCRP expression in PDAC may be a useful test in identifying a subgroup of patients with a poor prognosis.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Korea.
authors.forename: Sang Hyub
authors.initials: SH
authors.lastname: Lee
authors.forename: Haeryoung
authors.initials: H
authors.lastname: Kim
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Jai Young
authors.initials: JY
authors.lastname: Cho
authors.forename: Yoo-Seok
authors.initials: YS
authors.lastname: Yoon
authors.forename: Ho-Seong
authors.initials: HS
authors.lastname: Han
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C114462:multidrug resistance-associated protein 3