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.

Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflicts to disclose.

Published by Elsevier Inc.

Figures

FIGURE 1

ERCC1 expression in ovarian carcinoma. A) Serous ovarian carcinoma with negative immunoexpression of ERCC1 (original magnification 400X). B) Strong nuclear immunoexpression of ERCC1 in tumor cells only, with surrounding stroma negative (original magnification 400X).

FIGURE 2

Kaplan-Meier estimates of progression-free survival (PFS) between women whose tumors stained positive versus those whose tumors stained negative for ERCC1: (A) analysis from combined data of two protocols; (B) analysis from GOG-172; and (C) analysis from GOG-182.

FIGURE 2

Kaplan-Meier estimates of progression-free survival (PFS) between women whose tumors stained positive versus those whose tumors stained negative for ERCC1: (A) analysis from combined data of two protocols; (B) analysis from GOG-172; and (C) analysis from GOG-182.

FIGURE 3

Kaplan-Meier estimates of overall survival (OS) between women whose tumors stained positive versus those whose tumors stained negative for ERCC1: (A) analysis from combined data of two protocols; (B) analysis from GOG-172; and (C) analysis from GOG-182.

FIGURE 3

Kaplan-Meier estimates of overall survival (OS) between women whose tumors stained positive versus those whose tumors stained negative for ERCC1: (A) analysis from combined data of two protocols; (B) analysis from GOG-172; and (C) analysis from GOG-182.

FIGURE 4

Associations of ERCC1 Expression and Genetic Polymorphisms (codon118 and C8092A)