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Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer.
Nomura, Hiroyuki; Kataoka, Fumio; Aoki, Daisuke; Jinno, Hiromitsu; Kitagawa, Yuko; Sato, Yuji; Womack, Chris; Wombwell, Helen; Hodgson, Darren; O'Connor, Mark; Harbron, Chris; Yin, Xiaolu.
Afiliação
  • Nomura H; Keio University School of Medicine, Tokyo, Japan.
  • Kataoka F; Keio University School of Medicine, Tokyo, Japan.
  • Aoki D; Keio University School of Medicine, Tokyo, Japan.
  • Jinno H; Keio University School of Medicine, Tokyo, Japan.
  • Kitagawa Y; Keio University School of Medicine, Tokyo, Japan.
  • Sato Y; Keio University School of Medicine, Tokyo, Japan.
  • Womack C; AstraZeneca, Macclesfield, UK.
  • Wombwell H; AstraZeneca, Macclesfield, UK.
  • Hodgson D; AstraZeneca, Macclesfield, UK.
  • O'Connor M; AstraZeneca, Macclesfield, UK.
  • Harbron C; AstraZeneca, Macclesfield, UK.
  • Yin X; Histopathology, Department of Translational Science, Asia & Emerging Markets IMED, AstraZeneca R&D, Shanghai, China.
Cancer Biomark ; 16(1): 145-52, 2016.
Article em En | MEDLINE | ID: mdl-26577420
BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Biomarcadores Tumorais / Expressão Gênica / Reparo de DNA por Recombinação / Neoplasias de Mama Triplo Negativas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Cancer Biomark Assunto da revista: BIOQUIMICA / NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Japão País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Biomarcadores Tumorais / Expressão Gênica / Reparo de DNA por Recombinação / Neoplasias de Mama Triplo Negativas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Cancer Biomark Assunto da revista: BIOQUIMICA / NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Japão País de publicação: Holanda