title: CK8/18 expression, the basal phenotype, and family history in identifying BRCA1-associated breast cancer in the Ontario site of the breast cancer family registry.
abstract: BACKGROUND
  BRCA1-associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1-associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1-associated tumor profile in a pathologically well-characterized cohort would be improved.
  
  
  METHODS
  Fifty-eight patients with known BRCA1 germline mutations and 221 control (familial non-BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was abstracted. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best-subsets variable-selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1-associated tumors from non-BRCA associated tumors.
  
  
  RESULTS
  BRCA1-associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non-BRCA tumors, whether they were basal-like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1-associated cancers.
  
  
  CONCLUSIONS
  CK8/18 expression was independently associated with BRCA1-associated breast cancers. Reduced CK8/18 expression in conjunction with the basal-like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing.
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital and the Department of Laboratory Medicine, St. Michael's Hospital, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. mulligana@smh.toronto.on.ca.
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Mulligan
authors.forename: Dushanthi
authors.initials: D
authors.lastname: Pinnaduwage
authors.forename: Anita L
authors.initials: AL
authors.lastname: Bane
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Bull
authors.forename: Frances P
authors.initials: FP
authors.lastname: O'Malley
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism*; D053533:Keratin-8 / Q000378:metabolism*; D009864:Ontario; D010641:Phenotype; D012042:Registries
chemical_list: D014408:Biomarkers, Tumor; D053538:Keratin-18; D053533:Keratin-8