ERCC1 RNA expression in peripheral blood predicts minor histopathological response to neoadjuvant radio-chemotherapy in patients with locally advanced cancer of the esophagus

J Gastrointest Surg. 2008 Nov;12(11):1815-21. doi: 10.1007/s11605-008-0668-7. Epub 2008 Sep 3.

Abstract

Objective: The aim of this study was to determine the gene is spelled excision repair cross-complementing gene 1 (ERCC1) RNA-expression in peripheral blood as a non-invasive molecular predictor of response to neoadjuvant radio-chemotherapy in patients with locally advanced cancer of the esophagus.

Background: Only patients with locally advanced cancer of the esophagus with a major histopathological response to neoadjuvant radio-chemotherapy benefit from this treatment. No non-invasive molecular marker exists that can reliably predict response to neoadjuvant therapy in this disease. To improve the treatment of patients with cancer of the esophagus, molecular predictors of response are desperately needed.

Methods: Blood samples were drawn from 29 patients with esophageal cancer prior to neoadjuvant radio-chemotherapy. After extraction of cellular tumor-RNA from blood samples, quantitative expression analysis of ERCC1 was done by real-time reverse transcription polymerase chain reaction.

Results: Nineteen (65.5%) patients showed a minor and ten (34.5%) a major histopathological response to neoadjuvant therapy. ERCC1 expression in blood of patients was detectable in 82.8%. The median ERCC1 expression was 0.62 (minimum 0.00, maximum 2.48) in minor responders and 0.24 (minimum 0.00, maximum 0.45) in major responders (p = 0.004). No significant associations were detectable between ERCC1 levels and patients' clinical variables. Relative ERCC1 levels above 0.452 were not associated with major histopathological response (sensitivity, 68.4; specificity, 100%), and 13 of 19 patients with minor response could be unequivocally identified.

Conclusion: Minor responders to the applied therapy show a significant higher ERCC1 expression level in their blood compared to major responders. ERCC1 appears to be a highly specific non-invasive predictor of response to neoadjuvant therapy in esophageal cancer.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Chemotherapy, Adjuvant
  • DNA-Binding Proteins / blood*
  • DNA-Binding Proteins / genetics
  • Endonucleases / blood*
  • Endonucleases / genetics
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Esophagectomy / methods
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Probability
  • Prognosis
  • Prospective Studies
  • RNA, Neoplasm / blood*
  • RNA, Neoplasm / genetics
  • ROC Curve
  • Radiotherapy, Adjuvant
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment
  • Sampling Studies
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • RNA, Neoplasm
  • ERCC1 protein, human
  • Endonucleases