title: Differential expression of ERCC1 in pancreas adenocarcinoma: high tumor expression is associated with earlier recurrence and shortened survival after resection.
abstract: BACKGROUND
  Increased tumor expression of excision repair cross-complementing gene-1 (ERCC1) is associated with decreased survival in patients with various cancers. Its effect in pancreatic adenocarcinoma (PAC) is not defined.
  
  
  METHODS
  Ninety-five patients were selected from a prospective database of all patients (n = 220) who underwent pancreaticoduodenectomy for PAC between January 2000 and October 2008. Tumor was isolated to perform immunohistochemistry for ERCC1 expression and was graded by a single pathologist. Main outcomes were recurrence-free survival (RFS) and overall survival (OS).
  
  
  RESULTS
  Median age was 63 years; 50 patients (53%) were male and 73 (77%) received adjuvant chemotherapy. Median follow-up was 25 months. Median RFS and OS was 9 and 16 months. Median tumor size was 3 cm; 26% had a positive resection margin, 34% had poorly differentiated tumors, 61% had positive lymph nodes, 88% had perineural invasion, and 45% had lymphovascular invasion. Tumors exhibited differential ERCC1 expression in terms of intensity staining [none-weak: 61%; moderate-strong: 39%], percentage staining [0: 39%; 1-10: 29%; 11-50: 20%; 51-100: 12%], and overall expression [low: 84%; high: 16%]. High ERCC1 expression was associated with reduced RFS (6 vs. 10 months; P = 0.03) and decreased OS (9 vs. 18 months; P = 0.019). After accounting for adverse tumor factors, high ERCC1 expression persisted as a negative prognostic factor on multivariate Cox regression for both RFS and OS [hazards ratio (HR), 2.1; 95% confidence interval (CI), 1.1-3.9; P = 0.02; HR, 3; 95% CI, 1.6-6; P = 0.001, respectively]. A subset analysis of only those 73 patients who received adjuvant therapy revealed the same negative effect of high ERCC1 expression on RFS (4 vs. 15 months; P = 0.001) and OS (9 vs. 20 months; P < 0.001).
  
  
  CONCLUSIONS
  Pancreas cancer exhibits differential expression of ERCC1. High ERCC1 expression is associated with both reduced RFS and OS after resection. ERCC1 expression levels may help to predict patient outcome with adjuvant chemotherapy.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA. smaithe@emory.edu
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.forename: Ipek
authors.initials: I
authors.lastname: Coban
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kneuertz
authors.forename: David A
authors.initials: DA
authors.lastname: Kooby
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.forename: John S
authors.initials: JS
authors.lastname: Kauh
authors.forename: Juan
authors.initials: J
authors.lastname: Sarmiento
authors.forename: Charles A
authors.initials: CA
authors.lastname: Staley
authors.forename: N
authors.initials: N
authors.lastname: Volkan Adsay
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D004268:DNA-Binding Proteins; D003841:Deoxycytidine; C071447:ERCC1 protein, human; D004720:Endonucleases; D005472:Fluorouracil; D000093542:Gemcitabine