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Gynecol Oncol ; 125(2): 421-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22261301

RESUMO

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.


Assuntos
Biomarcadores Tumorais/biossíntese , Proteínas de Ligação a DNA/biossíntese , Endonucleases/biossíntese , Neoplasias Epiteliais e Glandulares/enzimologia , Neoplasias Ovarianas/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Cisplatino/administração & dosagem , Terapia Combinada , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Intervalo Livre de Doença , Endonucleases/genética , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Paclitaxel/administração & dosagem , Inclusão em Parafina , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
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