title: Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy.
abstract: BACKGROUND
  Tumor expression of excision cross-complementing gene-1 (ERCC1), human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunit M1 (RRM1), and ribonucleotide reductase subunit M2 (RRM2), is associated with the efficacy of platinum and gemcitabine chemotherapy. The authors of this report recently demonstrated that high ERCC1 and RRM2 expression levels are independent negative prognostic markers for survival in early stage pancreas cancer. The differential expression and prognostic value of these biomarkers in biliary tract malignancy (BTM) is unknown.
  
  
  METHODS
  In total, 63 patients who had tissue available for analysis were selected from a prospective database of all patients (n = 104) who underwent resection of BTM (intrahepatic, hilar, or distal cholangiocarcinoma; gallbladder carcinoma) between January 2000 and December 2008. Immunohistochemistry for ERCC1, hENT1, RRM1, and RRM2 expression was performed. Staining was scored by a single pathologist who was blinded to patient outcomes.
  
  
  RESULTS
  The median patient age was 67 years. The median overall survival (OS) was 16.2 months, and the median follow-up was 32.7 months. Only 3 BTMs (4.8%) had high ERCC1 expression, and 92.1% and 81% of BTMs exhibited high hENT1 and RRM1 expression, respectively. RRM2 expression varied, and 32% of tumors demonstrated high RRM2 expression. ERCC1 and RRM1 were not associated with OS. High RRM2 expression was associated with a trend toward improved OS (30.8 months vs 16.2 months; P = .06), and high hENT1 expression was associated with improved OS (17.7 months vs 9.5 months; P = .04).
  
  
  CONCLUSIONS
  Most BTMs exhibited low ERCC1 expression and high hENT1 and RRM1 expression, whereas RRM2 expression levels varied. High expression of hENT1 was associated with improved OS. These findings may have implications for the selection of chemotherapy agents (gemcitabine vs platinum) and the stratification of patients in chemotherapy trials that assess outcome.
authors: Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.
authors: Sarah B
authors: SB
authors: Fisher
authors: Kevin E
authors: KE
authors: Fisher
authors: Sameer H
authors: SH
authors: Patel
authors: Matthew G
authors: MG
authors: Lim
authors: David A
authors: DA
authors: Kooby
authors: Bassel F
authors: BF
authors: El-Rayes
authors: Charles A
authors: CA
authors: Staley
authors: N Volkan
authors: NV
authors: Adsay
authors: Alton B
authors: AB
authors: Farris
authors: Shishir K
authors: SK
authors: Maithel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D001661:Biliary Tract Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000378:metabolism*; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012262:Ribonucleoside Diphosphate Reductase / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D025521:Tumor Suppressor Proteins; C093713:ribonucleotide reductase M2; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases