title: Pattern of breast cancer susceptibility gene 1 expression is a potential prognostic biomarker in resectable pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  The tumor-suppressor breast cancer susceptibility gene 1 (BRCA1) is a nuclear-cytoplasmic shuttling protein that when in the nucleus is required for DNA repair whereas when in the cytoplasm is important in activating cell death processes. Although BRCA1 mutations have been shown to be associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC), its role in disease progression is yet to be determined. We hypothesized that BRCA1 expression pattern could be used as a prognostic biomarker.
  
  
  METHODS
  Sixty-seven patients who underwent resections for PDAC were included. A tissue microarray was constructed, stained with antibodies to BRCA1, and scored for intensity and subcellular location. Univariate and multivariate statistical analyses were performed.
  
  
  RESULTS
  An increase in cytosolic BRCA1 distribution was associated with higher pathologic stage (P = 0.006). Nuclear-cytosolic BRCA1 distribution was associated with a decrease in recurrence-free survival with a hazards ratio of 1.4 (P = 0.059). Decreased BRCA1 intensity was associated with higher pathologic stage (P = 0.027), but BRCA1 intensity was not associated with overall survival or recurrence-free survival.
  
  
  CONCLUSIONS
  Our results demonstrate a possible association of BRCA1 expression pattern with pathologic stage, implying a potential role of BRCA1 in PDAC development and progression.
authors.affiliation: Department of Radiation Oncology, School of Medicine,Vanderbilt University, Nashville, TN, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Sabrina C
authors.initials: SC
authors.lastname: Wentz
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Ausborn
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Nipun
authors.initials: N
authors.lastname: Merchant
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: A Bapsi
authors.initials: AB
authors.lastname: Chakravarthy
authors.forename: Fen
authors.initials: F
authors.lastname: Xia
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000368:Aged; D019313:BRCA1 Protein / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor