Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy

Br J Cancer. 2010 May 25;102(11):1600-7. doi: 10.1038/sj.bjc.6605686. Epub 2010 May 11.

Abstract

Aims: Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro-oesophageal adenocarcinoma. Previously, we validated the utility of the tumour regression grade (TRG) as a histopathological marker of tumour downstaging in patients receiving platinum-based neoadjuvant chemotherapy. In this study we profiled key DNA repair and damage signalling factors and correlated them with clinicopathological outcomes, including TRG response.

Methods and results: Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays (TMAs). The first set consisted of 142 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 103 gastric/gastro-oesophageal cancer cases exposed to preoperative platinum-based chemotherapy. Expressions of ERCC1, XPF, FANCD2, APE1 and p53 were investigated using immunohistochemistry. In patients who received neoadjuvant chemotherapy, favourable TRG response (TRG 1, 2 or 3) was associated with improvement in disease-specific survival (P=0.038). ERCC1 nuclear expression correlated with lack of histopathological response (TRG 4 or 5) to neoadjuvant chemotherapy (P=0.006) and was associated with poor disease-specific (P=0.020) and overall survival (P=0.040).

Conclusions: We provide evidence that tumour regression and ERCC1 nuclear protein expression evaluated by immunohistochemistry are promising predictive markers in gastro-oesophageal cancer patients receiving neoadjuvant platinum-based chemotherapy.

Publication types

  • Evaluation Study

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Pharmacological / analysis
  • Biomarkers, Pharmacological / metabolism
  • Biomarkers, Tumor / metabolism
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / metabolism*
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Platinum Compounds / administration & dosage
  • Prognosis
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Tissue Array Analysis
  • Treatment Outcome
  • Tumor Burden / physiology*

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Platinum Compounds
  • ERCC1 protein, human
  • Endonucleases