Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: A gynecologic oncology group study

Jennifer M. Rubatt, Kathleen M. Darcy, Chunqiao Tian, Franco Muggia, Rajiv Dhir, Deborah K. Armstrong, Michael A. Bookman, Laura J. Niedernhofer, Julie Deloia, Michael Birrer, Thomas Carl Krivak

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Objective: Excision repair cross-complementation group 1 (ERCC1) is required for the repair of platinum-induced DNA damage. This study sought to assess the prognostic value of ERCC1 expression, measured by immunohistochemistry (IHC) using a highly specific antibody, in advanced epithelial ovarian cancer (EOC) patients treated with platinum-based chemotherapy. Methods: Formalin-fixed, paraffin-embedded tumors were collected from two GOG phase III trials (GOG-172 and GOG-182) of patients with stage III/IV EOC treated with platinum-based chemotherapy. ERCC1 was detected by (IHC) using FL297 polyclonal antibody and tumors were categorized as negative or positive, based on nuclear staining of tumor cells. ERCC1 genotyping was performed as previously reported. Associations between ERCC1 expression and clinical characteristics, platinum responsiveness, progression-free survival (PFS) or overall survival (OS) were evaluated. Results: Of 408 eligible patients, 27% had tumors that were ERCC1 positive. ERCC1 expression was not associated with clinical characteristics or platinum-responsiveness. Women with ERCC1-positive versus -negative tumors had similar median PFS (17.9 months versus 17.5 months, respectively, p = 0.59), median OS (52.0 months versus 47.0 months, respectively, p = 0.30), risk of disease progression (adjusted hazard ratio [HR] = 0.90, 95% confidence interval (CI): 0.71-1.15, p = 0.41), and risk of death (adjusted HR = 0.81, 95% CI: 0.61-1.07, p = 0.14). ERCC1 expression, as measured by IHC, was not associated with single nucleotide polymorphisms (SNPs), in codon 118 and C8092A, of the ERCC1 gene. Conclusions: ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalGynecologic oncology
Volume125
Issue number2
DOIs
StatePublished - May 2012
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office ( CA 27469 ), the Gynecologic Oncology Group Statistical and Data Center ( CA 37517 ). This project used the University of Pittsburgh Cancer Institute Tissue and Research Pathology Services and was supported in part by award P30CA047904 . L.J.N. and J.M.R. were supported by NIEHS ( ES016114 ). The following Gynecologic Oncology Group member institutions participated in this study: Roswell Park Cancer Institute, University of Alabama at Birmingham, Duke University Medical Center, Abington Memorial Hospital, Walter Reed Army Medical Center, University of Minnesota Medical School, University of Mississippi Medical Center, Colorado Gynecologic Oncology Group P.C., University of California at Los Angeles, University of Washington, University of Pennsylvania Cancer Center, Milton S. Hershey Medical Center, University of Cincinnati, University of North Carolina School of Medicine, University of Iowa Hospitals and Clinics, University of Texas Southwestern Medical Center at Dallas, Indiana University School of Medicine, Wake Forest University School of Medicine, University of California Medical Center at Irvine, Tufts-New England Medical Center, Rush-Presbyterian-St. Luke's Medical Center, Magee Women's Hospital, SUNY Downstate Medical Center, University of Kentucky, The Cleveland Clinic Foundation, State University of New York at Stony Brook, Southwestern Oncology Group, Washington University School of Medicine, Cooper Hospital/University Medical Center, Columbus Cancer Council, MD Anderson Cancer Center, University of Massachusetts Medical School, Fox Chase Cancer Center, Women's Cancer Center, University of Oklahoma, University of Virginia Health Sciences Center, University of Chicago, Tacoma General Hospital, Thomas Jefferson University Hospital, Mayo Clinic, Case Western Reserve University, Tampa Bay Cancer Consortium, North Shore University Hospital, Gynecologic Oncology Network, Ellis Fischel Cancer Center, Fletcher Allen Health Care, Australia New Zealand GOG, Southern Nevada CCOP, Yale University, University of Wisconsin Hospital, Cancer Trials Support Unit, University of Texas Galveston, Southeast Gynecologic Oncology, Community Clinical Oncology Program, MRC-United Kingdom, and Mario Negri.

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

Keywords

  • Biomarker
  • DNA repair
  • Ovarian cancer
  • Platinum-resistance
  • Prognosis

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