Predictive value of ERCC1, ERCC2, and XRCC1 overexpression for stage III colorectal cancer patients receiving FOLFOX-4 adjuvant chemotherapy

J Surg Oncol. 2013 Dec;108(7):457-64. doi: 10.1002/jso.23422. Epub 2013 Aug 31.

Abstract

Objectives: To determine the correlation between expression of three DNA repair genes and early failure/clinical outcome of stage III colorectal cancer (CRC) patients administrated with FOLFOX-4, including the excision repair cross-complementation group 1 (ERCC1), the excision repair cross-complementing 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1).

Materials and methods: We retrospectively analyzed clinicopathological features and ERCC1, ERCC2, XRCC1 expressions by immunohistochemical staining in 180 stage III CRC patients undergoing curative resection and treated with FOLFOX-4 chemotherapy to identify predictors of postoperative early failure.

Results: Among 180 CRC patients, 44 patients were classified into early failure group, and 136 patients were categorized into non-early failure group. A multivariate logistic regression analysis showed that ERCC1 overexpression (P = 0.005), and high postoperative carcinoembryonic antigen (CEA) levels (P = 0.001) were independent predictors of early failure. Additionally, ERCC1 overexpression was not only a predictor of early failure but also for disease-free survival (P < 0.001) and overall survival (P < 0.001). However, no predictive roles of ERCC2 and XRCC1 expression among these analyzed patients.

Conclusions: ERCC1 overexpression is an important predictor of early failure in patients with stage III CRC administrating FOLFOX-4 adjuvant chemotherapy and this marker may help identify patients who would benefit from intensive follow-up and enhance therapeutic programs.

Keywords: ERCC1; FOLFOX-4; early failure; stage III colorectal cancer; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • DNA Repair
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Disease-Free Survival
  • Endonucleases / biosynthesis*
  • Endonucleases / genetics
  • Female
  • Fluorouracil / administration & dosage
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Retrospective Studies
  • Treatment Outcome
  • X-ray Repair Cross Complementing Protein 1
  • Xeroderma Pigmentosum Group D Protein / biosynthesis*
  • Xeroderma Pigmentosum Group D Protein / genetics

Substances

  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • ERCC1 protein, human
  • Endonucleases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol