Impact of ERCC1 expression on treatment outcome in small-cell lung cancer patients treated with platinum-based chemotherapy

Eur J Cancer. 2012 Dec;48(18):3378-85. doi: 10.1016/j.ejca.2012.06.011. Epub 2012 Jul 12.

Abstract

Introduction: The excision repair cross-complementing 1 (ERCC1) protein is an extensively investigated molecular marker because it may decrease sensitivity to platinum-based chemotherapy. Low ERCC1 expression has already been correlated with better treatment efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy. However, the data on a prognostic and/or predictive value of ERCC1 in small-cell lung cancer (SCLC) are still very limited.

Methods: This retrospective pilot study evaluated the impact of ERCC1 expression levels on response to first-line platinum-based chemotherapy with or without radiotherapy and survival outcomes of 77 SCLC patients. ERCC1 protein expression was determined immunohistochemically in primary tumour tissue.

Results: ERCC1 protein expression was positive in 40/77 (51.9%) of our patients. No significant association was found between ERCC1 protein expression and response rate to first-line platinum-based chemotherapy, progression-free survival (PFS), or overall survival (OS), either in the overall population or in patients stratified by disease stage.

Conclusions: In our limited group of 77 SCLC patients, ERCC1 protein expression was not found to correlate with either response rate to platinum-based chemotherapy or survival outcomes. Multi-centric prospective trials using a validated method of ERCC1 determination are mandatory in order to obtain a definitive answer on the predictive value of ERCC1 in SCLC.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / antagonists & inhibitors*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / enzymology
  • Carcinoma, Small Cell / mortality
  • Carcinoma, Small Cell / radiotherapy
  • Chemoradiotherapy
  • Cisplatin / administration & dosage
  • Cisplatin / antagonists & inhibitors*
  • Cisplatin / pharmacology
  • DNA Repair*
  • DNA, Neoplasm / drug effects
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Disease-Free Survival
  • Endonucleases / biosynthesis
  • Endonucleases / genetics
  • Endonucleases / physiology*
  • Epirubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Pilot Projects
  • Prognosis
  • Retrospective Studies
  • Single-Blind Method
  • Slovenia / epidemiology
  • Topotecan / administration & dosage
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Antineoplastic Agents, Alkylating
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Epirubicin
  • Vincristine
  • Etoposide
  • Topotecan
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin