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Chen, Y.T. et al.

Yao-Tseng Chen, Dara S. Ross, Rita Chiu, Xi K. Zhou, Yunn-Yi Chen, Peishan Lee, Syed A. Hoda, Andrew J. Simpson, Lloyd J. Old, Otavia Caballero, A. Munro Neville,

Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers.

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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.[1]

References

Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers. Chen, Y.T., Ross, D.S., Chiu, R., Zhou, X.K., Chen, Y.Y., Lee, P., Hoda, S.A., Simpson, A.J., Old, L.J., Caballero, O., Neville, A.M. PLoS. ONE (2011) [Pubmed]

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