title: Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers.
abstract: BACKGROUND
  Cancer/testis (CT) antigens are protein antigens normally expressed only in germ cells of testis, and yet are expressed in a proportion of a wide variety of human cancers. CT antigens can elicit spontaneous immune responses in cancer patients with CT-positive cancers, and CT antigen-based therapeutic cancer vaccine trials are ongoing for "CT-rich" tumors. Although some previous studies found breast cancer to be "CT-poor", our recent analysis identified increased CT mRNA transcripts in the ER-negative subset of breast cancer.
  
  
  RESULTS
  In this study, we performed a comprehensive immunohistochemical study to investigate the protein expression of eight CT genes in 454 invasive ductal carcinomas, including 225 ER/PR/HER2-negative (triple-negative) carcinomas. We found significantly more frequent expression of all eight CT antigens in ER-negative cancers, and five of them--MAGEA, CT7, NY-ESO-1, CT10 and CT45, were expressed in 12-24% of ER-negative cancers, versus 2-6% of ER-positive cancers (p<0.001 to 0.003). In comparison, GAGE, SAGE1 and NXF2 were only expressed in 3-5% of ER-negative and 0-2% of ER-positive cancers. ER-negative cancers were also more likely to simultaneously co-express multiple CT antigens, with 27% (34/125) of ER-negative, CT-positive tumors expressing three or more CT antigens. HER2 status had no consistent effect on CT expression, and triple-negative carcinomas showed similar frequencies of MAGEA and NY-ESO-1 expression as ER-negative/HER2-positive carcinomas. More frequent CT expression was also found in tumors with higher nuclear grade (p<0.001 to p = 0.01) and larger in size (>2 cm).
  
  
  CONCLUSIONS
  CT antigens are preferentially expressed in hormone receptor-negative and high-grade breast cancer. Considering the limited treatment options for ER/PR/HER2 triple-negative breast cancer, the potential of CT-based immunotherapy should be explored.
authors: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, United States of America. ytchen@med.cornell.edu
authors: Yao-Tseng
authors: YT
authors: Chen
authors: Dara S
authors: DS
authors: Ross
authors: Rita
authors: R
authors: Chiu
authors: Xi K
authors: XK
authors: Zhou
authors: Yunn-Yi
authors: YY
authors: Chen
authors: Peishan
authors: P
authors: Lee
authors: Syed A
authors: SA
authors: Hoda
authors: Andrew J
authors: AJ
authors: Simpson
authors: Lloyd J
authors: LJ
authors: Old
authors: Otavia
authors: O
authors: Caballero
authors: A Munro
authors: AM
authors: Neville
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone