title: Predictive and prognostic values of ERCC1 and XRCC1 in biliary tract cancers.
abstract: OBJECTIVE
  To investigate the predictive and prognostic values of DNA repair genes excision repair cross-complementation group 1 (ERCC1) and X-ray repair cross-complementing group 1 (XRCC1) in tumour samples from patients with a diagnosis of biliary tract cancer (BTC).
  
  
  METHODS
  Expressions of ERCC1 and XRCC1 were determined by immunohistochemistry (IHC) for 160 patients with BTC and association with clinicopathological features and patient survival was performed to evaluate their predictive and prognostic values.
  
  
  RESULTS
  Neoplastic tissue showed much lower nuclear expression compared with non-neoplastic tissue for ERCC1 (median immunostaining score (IS)=0.7 (95% CI 0.2 to 1.3) vs 8.0 (95% CI 5.5 to 8.0), p<0.001) and XRCC1 (median IS=4.0 (95% CI 3.0 to 5.5) vs 8.0 (95% CI 8.0 to 12.0), p<0.001). High nuclear expression of both proteins was able to predict better overall survival (OS) in patients with gallbladder adenocarcinoma, distal bile duct and perihilar cholangiocarcinoma undergoing gemcitabine as adjuvant therapy (ERCC1: median OS estimate=39.7 vs 22.9 months, p=0.011; XRCC1: median OS estimate=33.8 vs 14.6 months, p=0.005). Intense cytoplasmic expression of XRCC1 was found in 12 patients; these patients had significantly more frequent lymph node metastasis (90.0% vs 48.1%, p=0.017) and worse OS (median estimate=12.6 months vs 25.6 months, p=0.004) and recurrence-free survival (median estimate=5.7 months vs 15.1 months, p=0.011). Vascular invasion was significantly more frequent in patients with low nuclear expression for ERCC1 (58.7% vs 20.9%, p<0.001) and XRCC1 (69.6% vs 30.3%, p=0.001).
  
  
  CONCLUSIONS
  IHC expression of ERCC1 and XRCC1 has some predictive and prognostic values in patients with BTC. Nuclear expression of ERCC1 and XRCC1 may be used to predict therapeutic response in patients undergoing gemcitabine monotherapy.
authors.affiliation: Department of Pathology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Muhtashim
authors.initials: M
authors.lastname: Mian
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada Department of Medical Oncology, The Christie NHS Foundation Trust/Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: Mairéad G
authors.initials: MG
authors.lastname: McNamara
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Doherty
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Hedley
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Department of Pathology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stefano
authors.initials: S
authors.lastname: Serra
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000076105:X-ray Repair Cross Complementing Protein 1; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D003841:Deoxycytidine; C071447:ERCC1 protein, human; D004720:Endonucleases; D000093542:Gemcitabine
keywords: BILIARY; CANCER; IMMUNOHISTOCHEMISTRY