title: Distinct claudin expression characterizes BRCA1-related breast cancer.
abstract: OBJECTIVE
  Members of the claudin family are involved in cancer progression and are differentially expressed in subtypes of breast cancer. Breast cancers in BRCA1 germ line mutation carriers have distinct clinicopathological characteristics. Biomarkers that discriminate between BRCA1-related and sporadic breast cancer cases are needed to improve early identification of mutation carriers. In this study we evaluated protein expression of five major claudins in BRCA1-related breast cancers in comparison with sporadic controls.
  
  
  RESULTS
  Forty breast cancers in BRCA1 mutation carriers and 40 age-matched sporadic breast cancers were immunohistochemically stained for claudins 1, 3, 4, 6 and 7. Total intratumoural expression levels were compared to those in the surrounding normal tissue. In addition, subcellular claudin expression was scored. Higher overexpression rates were observed for all five claudins in BRCA1-related breast cancers when compared to sporadic controls. In multivariate analysis, overexpression of claudin 3, 4, and 7 was mainly dependent on ER-status, whereas overexpression of claudin 6 and high membranous expression of claudin 1 were independent of other characteristics.
  
  
  CONCLUSIONS
  BRCA1-related breast cancers are characterized by frequent overexpression of claudins. Especially claudin 1 and 6 expression may help to discriminate mutation carriers from sporadic breast cancer cases.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marise R
authors.initials: MR
authors.lastname: Heerma van Voss
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Yvonne H C M
authors.initials: YH
authors.lastname: Smolders
authors.forename: Joost
authors.initials: J
authors.lastname: Bart
authors.forename: Elsken
authors.initials: E
authors.lastname: van der Wall
authors.forename: Petra
authors.initials: P
authors.lastname: van der Groep
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057167:Claudins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor; D057167:Claudins
keywords: BRCA1 protein; claudins; familial breast cancer