ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients

J Natl Cancer Inst. 1992 Oct 7;84(19):1512-7. doi: 10.1093/jnci/84.19.1512.

Abstract

Background: ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents.

Purpose: Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance.

Methods: Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene.

Results: Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders.

Conclusion: We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase.

MeSH terms

  • Blotting, Southern
  • Carboplatin / therapeutic use
  • Cisplatin / therapeutic use
  • Cohort Studies
  • DNA Helicases*
  • DNA Probes
  • DNA-Binding Proteins*
  • Endonucleases*
  • Female
  • Gene Expression*
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Proteins / analysis*
  • RNA, Neoplasm / analysis
  • Remission Induction
  • Transcription Factors*
  • Xeroderma Pigmentosum Group D Protein

Substances

  • DNA Probes
  • DNA-Binding Proteins
  • Proteins
  • RNA, Neoplasm
  • Transcription Factors
  • Carboplatin
  • ERCC1 protein, human
  • Endonucleases
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Cisplatin