Literature DB >> 22261301

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 Rubatt1, 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.   

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. Published by Elsevier Inc.

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Year:  2012        PMID: 22261301      PMCID: PMC3490188          DOI: 10.1016/j.ygyno.2012.01.008

Source DB:  PubMed          Journal:  Gynecol Oncol        ISSN: 0090-8258            Impact factor:   5.482


  34 in total

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2.  Intraperitoneal cisplatin and paclitaxel in ovarian cancer.

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6.  Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells.

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Review 4.  Platinum-resistant ovarian cancer: From drug resistance mechanisms to liquid biopsy-based biomarkers for disease management.

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9.  High ERCC1 expression is associated with platinum-resistance, but not survival in patients with epithelial ovarian cancer.

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10.  Functional characterization of a novel transcript of ERCC1 in chemotherapy resistance of ovarian cancer.

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