title: Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma.
abstract: BACKGROUND
  Although multidrug resistance protein 2 (MRP2) confers chemoresistance in some cancer types, its implication on oesophageal squamous cell carcinoma (ESCC) remains unclear.
  
  
  METHODS
  We evaluated MRP2 expression by immunohistochemistry and RT-PCR using 81 resected specimens from ESCC patients who did or did not receive neo-adjuvant chemotherapy (NACT), including 5-fluorouracil, doxorubicin, and cisplatin (CDDP). Correlation between MRP2 expression and response to chemotherapy was also examined in 42 pre-therapeutic biopsy samples and eight ESCC cell lines.
  
  
  RESULTS
  MRP2-positive immunostaining was more frequently observed in ESCCs with NACT than in those without NACT (27.3 vs 5.4%). The MRP2-positive patients showed poorer prognosis than MRP2-negative patients (5-year survival rate, 25.6 vs 55.7%). Concordantly, ESCC with NACT showed 2.1-fold higher mRNA expression of MRP2 than those without NACT (P=0.0350). In pre-therapeutic biopsy samples of patients with NACT, non-responders showed 2.9-fold higher mRNA expression of MRP2 than responders (P=0.0035). Among the panel of ESCC cell lines, TE14 showed the highest MRP2 mRNA expression along with the strongest resistance to CDDP. Inhibition of MRP2 expression by small-interfering RNA reduced chemoresistance to CDDP.
  
  
  CONCLUSIONS
  Our data suggested that MRP2 is one of molecules, which regulate the sensitivity to chemotherapy including CDDP in advanced ESCC patients.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Makino
authors.forename: T
authors.initials: T
authors.lastname: Masuzawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kurokawa
authors.forename: H
authors.initials: H
authors.lastname: Miyata
authors.forename: S
authors.initials: S
authors.lastname: Takiguchi
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: N
authors.initials: N
authors.lastname: Matsuura
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020360:Neoadjuvant Therapy; D034741:RNA, Small Interfering / Q000494:pharmacology; D016019:Survival Analysis
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D002945:Cisplatin; D004317:Doxorubicin; D005472:Fluorouracil; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D034741:RNA, Small Interfering; C000715087:ABCC2 protein, human