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 Kay Armstrong, Michael A. Bookman, Laura J. Niedernhofer, Julie Deloia, Michael Birrer, Thomas Carl Krivak

Research output: Contribution to journalArticle

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

Fingerprint

DNA Repair
Platinum
Neoplasms
Immunohistochemistry
Therapeutics
Drug Therapy
Disease-Free Survival
Ovarian epithelial cancer
Confidence Intervals
Neoplasm Antibodies
Survival
Antibodies
Codon
Paraffin
Formaldehyde
DNA Damage
Single Nucleotide Polymorphism
Disease Progression
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

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

In: Gynecologic Oncology, Vol. 125, No. 2, 05.2012, p. 421-426.

Research output: Contribution to journalArticle

Rubatt, Jennifer M. ; Darcy, Kathleen M. ; Tian, Chunqiao ; Muggia, Franco ; Dhir, Rajiv ; Armstrong, Deborah Kay ; Bookman, Michael A. ; Niedernhofer, Laura J. ; Deloia, Julie ; Birrer, Michael ; Krivak, Thomas Carl. / 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. In: Gynecologic Oncology. 2012 ; Vol. 125, No. 2. pp. 421-426.
@article{b4bd0f9291dd4a419f2395d8a6da2e14,
title = "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",
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.",
keywords = "Biomarker, DNA repair, Ovarian cancer, Platinum-resistance, Prognosis",
author = "Rubatt, {Jennifer M.} and Darcy, {Kathleen M.} and Chunqiao Tian and Franco Muggia and Rajiv Dhir and Armstrong, {Deborah Kay} and Bookman, {Michael A.} and Niedernhofer, {Laura J.} and Julie Deloia and Michael Birrer and Krivak, {Thomas Carl}",
year = "2012",
month = "5",
doi = "10.1016/j.ygyno.2012.01.008",
language = "English (US)",
volume = "125",
pages = "421--426",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes

T2 - A gynecologic oncology group study

AU - Rubatt, Jennifer M.

AU - Darcy, Kathleen M.

AU - Tian, Chunqiao

AU - Muggia, Franco

AU - Dhir, Rajiv

AU - Armstrong, Deborah Kay

AU - Bookman, Michael A.

AU - Niedernhofer, Laura J.

AU - Deloia, Julie

AU - Birrer, Michael

AU - Krivak, Thomas Carl

PY - 2012/5

Y1 - 2012/5

N2 - 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.

AB - 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.

KW - Biomarker

KW - DNA repair

KW - Ovarian cancer

KW - Platinum-resistance

KW - Prognosis

UR - http://www.scopus.com/inward/record.url?scp=84859570977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859570977&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2012.01.008

DO - 10.1016/j.ygyno.2012.01.008

M3 - Article

C2 - 22261301

AN - SCOPUS:84859570977

VL - 125

SP - 421

EP - 426

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -