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.
authors.affiliation: Division of Gynecologic Oncology, Magee-Womens Hospital, Pittsburgh, PA 15213, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rubatt
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Chunqiao
authors.initials: C
authors.lastname: Tian
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhir
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Armstrong
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bookman
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Niedernhofer
authors.forename: Julie
authors.initials: J
authors.lastname: Deloia
authors.forename: Michael
authors.initials: M
authors.lastname: Birrer
authors.forename: Thomas Carl
authors.initials: TC
authors.lastname: Krivak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D004720:Endonucleases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D017239:Paclitaxel / Q000008:administration & dosage; D016612:Paraffin Embedding; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin