title: Ribonucleotide reductase M1 expression in intrahepatic cholangiocarcinoma.
abstract: OBJECTIVE
  Ribonucleotide reductase M1 (RRM1) is a key molecule for gemcitabine resistance. This study evaluated the immunohistochemical expression of RRM1 in resected specimens of intrahepatic cholangiocarcinoma (ICC) and investigated the efficacy of gemcitabine-based neoadjuvant chemotherapy in relation to RRM1 expression in tumors.
  
  
  METHODS
  A retrospective analysis was conducted on 34 consecutive Japanese patients who underwent resection of ICC. Of the 34 patients, 2 were treated with neoadjuvant chemotherapy consisting of gemcitabine 800mg/m2 every 2 weeks to address extrahepatic tumor extension. Expression of RRM1 in tumor specimens was assessed using immunohistochemistry and was classified as either positive or negative.
  
  
  RESULTS
  RRM1-positive expression was detected in 19/34 (56%) tumor specimens. Two patients were treated with gemcitabine-based neoadjuvant chemotherapy; one had a tumor specimen showing RRM1-positive expression and showed a 14% tumor reduction rate (stable disease); another patient had a tumor showing RRM1-negative expression and showed a 68% tumor reduction rate (partial response). Surgical procedures planned before administration of neoadjuvant chemotherapy were performed in both patients.
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy with gemcitabine for locally advanced ICC was well tolerated and did not impair planned surgical resections. Tumor expression of RRM1 may determine the efficacy of gemcitabine-based chemotherapy for patients with ICC.
authors.affiliation: Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. wakait@med.niigata-u.ac.jp
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shirai
authors.forename: Jun
authors.initials: J
authors.lastname: Sakata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takamura
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Korita
authors.forename: Katsuki
authors.initials: K
authors.lastname: Muneoka
authors.forename: Masataka
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hatakeyama
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000032:analysis; D016009:Chi-Square Distribution; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012264:Ribonucleotide Reductases / Q000378:metabolism*; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D012264:Ribonucleotide Reductases