title: Development of serous ovarian cancer is associated with the expression of homologous recombination pathway proteins.
abstract: To investigate the expressions of key markers in the homologous recombination (HR) pathway and the correlation with clinicopathological parameters in serous ovarian cancer (SOC). We analyzed the protein expression of MRE11, MDC1, ATM, ATR and BRCA1 by immunohistochemistry (IHC) in 97 SOC samples, and correlated with clinical parameters including age, tumor grades, clinical stage, status of menstruation and chemotherapy. Low expression of MRE11 and MDC1 was detected in 14.4 % and 3.1 % of the patient samples, and negative expression of ATM, ATR and BRCA1 was found in 11.3 %, 6.3 % and 29.9 % of the patient samples, respectively. ATR deficiency was significantly associated with menopause (P = 0.025), strong expression of ATM (P = 0.017) and MRE11 (P = 0.040) with pre-menopausal SOC, strong expression of MRE11 (P = 0.016) with low tumor grade, and strong expression of BRCA1 (P = 0.015) with early clinical stage. In addition, low expression of MRE11 was strongly associated with negativity of ATR (P < 0.001) and BRCA1 (P = 0.004) Furthermore, ATR deficiency was associated with low expression of ATM (P = 0.028) and loss expression of BRCA1 (P = 0.009). Our results suggest that reduced expression or loss of proteins in HR pathway is associated with SOC development. Abnormality of MRE11 and BRCA1 are strongly associated with late clinical stage in SOC patients.
authors.affiliation: Innovation Center China, AstraZeneca Global R&D, Shanghai, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Ye
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yin
authors.forename: Yuan Jie Charles
authors.initials: YJ
authors.lastname: Liu
authors.forename: Qunsheng
authors.initials: Q
authors.lastname: Ji
authors.forename: Enfeng
authors.initials: E
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D019313:BRCA1 Protein / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D059765:Homologous Recombination; D006801:Humans; D007124:Immunoenzyme Techniques; D000076228:MRE11 Homologue Protein; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C413163:MDC1 protein, human; C121766:MRE11 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000076228:MRE11 Homologue Protein
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