title: ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.
abstract: BACKGROUND
  Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy.
  
  
  METHODS
  Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression.
  
  
  RESULTS
  Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group.
  
  
  CONCLUSIONS
  Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.
authors.affiliation: Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: Y J
authors.initials: YJ
authors.lastname: Fang
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.forename: Q J
authors.initials: QJ
authors.lastname: Ou
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D005472:Fluorouracil