title: Expression of cancer testis antigens in human BRCA-associated breast cancers: potential targets for immunoprevention?
abstract: BACKGROUND
  Novel breast cancer risk-reducing strategies for individuals with germline mutations of the BRCA1 and/or BRCA2 genes are urgently needed. Identification of antigenic targets that are expressed in early cancers, but absent in normal breast epithelium of these high-risk individuals, could provide the basis for the development of effective immunoprophylactic strategies. Cancer testis (CT) antigens are potential candidates because their expression is restricted to tumors, and accumulating data suggest that they play important roles in cellular proliferation, stem cell function, and carcinogenesis. The objective of this study was to examine the expression of CT antigens and their frequency in BRCA-associated breast cancers.
  
  
  METHODS
  Archived breast cancer tissues (n = 26) as well as morphologically normal breast tissues (n = 7) from women carrying deleterious BRCA 1 and/or 2 mutations were obtained for antigen expression analysis by immunohistochemistry. Expression of the following CT antigens was examined: MAGE-A1, MAGE-A3, MAGE-A4, MAGE-C1.CT7, NY-ESO-1, MAGE-C2/CT10, and GAGE.
  
  
  RESULTS
  CT antigens were expressed in 16/26 (61.5%, 95% CI 43-80%) of BRCA-associated cancers, including in situ tumors. Thirteen of twenty-six (50%) breast cancers expressed two or more CT antigens; three cancers expressed all seven CT antigens. MAGE-A was expressed in 13/26 (50%) of cancers, NY-ESO-1 was expressed in 10/26 (38%) of tumors. In contrast, none of the CT antigens were expressed in adjacent or contralateral normal breast epithelium (P = 0.003).
  
  
  CONCLUSIONS
  We report a high CT antigen expression rate in BRCA-associated breast cancer as well as the lack of expression of these antigens in benign breast tissue of carriers, identifying CT antigens as potential vaccine targets for breast cancer prevention in these high-risk individuals.
authors.affiliation: New York University Cancer Institute, New York University School of Medicine, 462 First Avenue, New York, NY 10016, USA. Sylvia.adams@nyumc.org
authors.forename: Sylvia
authors.initials: S
authors.lastname: Adams
authors.forename: Luba
authors.initials: L
authors.lastname: Greeder
authors.forename: Elsa
authors.initials: E
authors.lastname: Reich
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.forename: Denise
authors.initials: D
authors.lastname: Fosina
authors.forename: Nicole
authors.initials: N
authors.lastname: Hanson
authors.forename: Jodie
authors.initials: J
authors.lastname: Tassello
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
authors.forename: Sandra
authors.initials: S
authors.lastname: Demaria
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human