ERCC1 Predicting Chemoradiation Resistance and Poor Outcome in Oesophageal Cancer

Eur J Cancer. 2008 Jan;44(1):54-60. doi: 10.1016/j.ejca.2007.09.006. Epub 2007 Oct 31.

Abstract

We assessed whether expression of excision repair cross-complementation group 1 (ERCC1) and/or thymidylate synthase (TS) can predict clinical outcome after preoperative chemoradiotherapy (CRT) in patients with localised oesophageal cancer. Paraffin-embedded pretreatment tumour specimens collected by endoscopic biopsy from patients treated with preoperative CRT (5-fluorouracil/cisplatin or capecitabine/cisplatin plus radiation) were analysed by immunohistochemical assay. Between March 1993 and June 2005, 129 patients were treated with preoperative CRT followed by surgery; of these, 108 biopsy specimens were available for analysis, and 40% and 35% were positive for ERCC1 and TS, respectively. Patients with ERCC1-negative (p<0.001) or TS-negative (p=0.04) tumours were significantly more likely to achieve pathologic major response. In multivariate analysis, ERCC1 was the only independent variable predicting pathologic response (p<0.001). Patients with ERCC1-negative tumours showed tendencies toward prolonged overall survival (p=0.10) and event free survival (p=0.08). Prospective studies are required to determine the benefit of preoperative CRT in ERCC1-negative tumours.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Combined Modality Therapy
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / metabolism*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / radiotherapy
  • Esophagectomy / methods*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Prospective Studies
  • Regression Analysis
  • Risk Factors
  • Survival Analysis
  • Thymidylate Synthase / metabolism*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Thymidylate Synthase
  • ERCC1 protein, human
  • Endonucleases