title: Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer.
abstract: BACKGROUND
  Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a central role in DNA damage response (DDR. It undergoes phosphorylation by various DDR kinases at different serine residues, of which ser1524 is known to be specifically phosphorylated by ATM in response to genotoxic stress.
  
  
  METHODS
  We performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113 early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were treated by adjuvant cisplatin-based chemotherapy. Staining results were correlated with overall survival (OS), disease free survival (DFS) and with the occurrence of brain metastases.
  
  
  RESULTS
  BRCA1 S1524 nuclear positivity was significantly correlated with longer OS and DFS in stage I and II patients (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV patients (P<0.05). No significant correlation was found with brain metastases.
  
  
  CONCLUSIONS
  The results show that BRCA1 phosphorylaton, at least in ser1524, differentiates the fate of early and advanced NSCLC as well as response to chemotherapy, but the underlying mechanisms are not completely understood. Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and predictive marker for patients with NSCLC.
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.
authors.forename: Mariam
authors.initials: M
authors.lastname: Gachechiladze
authors.forename: Ivo
authors.initials: I
authors.lastname: Uberall
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Kolek
authors.forename: Jiri
authors.initials: J
authors.lastname: Klein
authors.forename: Veronika
authors.initials: V
authors.lastname: Krejci
authors.forename: Jitka
authors.initials: J
authors.lastname: Stastna
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.forename: Eddie
authors.initials: E
authors.lastname: Fridman
authors.forename: Josef
authors.initials: J
authors.lastname: Skarda
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000502:physiology; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D002945:Cisplatin