Can the analysis of ERCC1 expression contribute to individualized therapy in nasopharyngeal carcinoma?

Int J Radiat Oncol Biol Phys. 2011 Apr 1;79(5):1414-20. doi: 10.1016/j.ijrobp.2009.12.072. Epub 2010 Jun 3.

Abstract

Purpose: To analyze the expression of excision repair cross-complementation group 1 (ERCC1) protein in predicting the clinical outcome of nasopharyngeal carcinoma (NPC).

Methods and materials: The histologic specimens of 258 patients with Stage III to IVB nonkeratinizing NPC who were treated with radiotherapy alone (Group I) or concurrent-adjuvant chemoradiotherapy (Group II) were retrieved. Immunostaining on ERCC1 protein was performed. The relationship of ERCC1 expression and clinical outcomes was analyzed.

Results: The median ERCC1 score (proportion score of positively stained cells times intensity) was 200 (range, 0-300), and ERCC1 expression was defined as high if the score was above the median. In Group I high-score tumor had a statistically lower locoregional failure-free rate (LRFFR) compared with low-score tumor (p < 0.05) but not distant failure-free rate (DFFR) and overall survival (OS). In Group II no statistically differences were noted in LRFFR, DFFR and OS with regard to the ERCC1 expression. Resistance to cisplatin-containing chemotherapy in high-ERCC1 score tumor was not observed in Group II. Interestingly, low-score tumor in Group I achieved similar local and distant control compared with Group II. Multivariate analysis showed that ERCC1 score was an independent prognostic factor in LRFFR (p < 0.05) and approached statistical significance in failure-free survival (p = 0.08) and OS (p = 0.07). Tumor with high ERCC1 score had a 2-fold (95% confidence interval, 1.02-3.85) increased risk of locoregional failure. This may imply an association of ERCC1 expression with the repair of radiation damage.

Conclusions: High ERCC1 expression predicts poor locoregional control in NPC. Chemotherapy response is not affected by ERCC1 expression. Further validation is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma
  • Cisplatin / therapeutic use
  • DNA-Binding Proteins / analysis*
  • Drug Resistance, Neoplasm
  • Endonucleases / analysis*
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / chemistry
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy
  • Neoplasm Proteins / analysis*
  • Precision Medicine
  • Young Adult

Substances

  • DNA-Binding Proteins
  • Neoplasm Proteins
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin
  • Fluorouracil