Cancer/Testis (CT) Antigens Are Preferentially Expressed in Hormone Receptor Negative Breast Cancers and May Offer Therapeutic Targets
DS Ross, O Caballero, P Lee, E Riedel, SA Hoda, LJ Old, AM Neville, Y-T Chen. Weill Cornell Medical College, New York; Ludwig Institute for Cancer Research, New York; Memorial Sloan-Kettering Cancer Center, New York
Background: CT antigens are proteins normally expressed only in germ cells and yet are aberrantly activated in a wide array of human cancers. This makes them attractive targets for cancer immunotherapy and phase III clinical trials are ongoing for melanoma and lung cancer. In breast cancer, we recently showed that 2 CT antigens, MAGE-A and NY-ESO-1, were preferentially expressed in estrogen receptor (ER) negative tumors. To further investigate the characteristics of CT expression in breast cancer, we analyzed the expression of 8 CT antigens, correlating results to ER, progesterone receptor (PR), and HER2 status of these tumors.
Design: A tissue microarray of 40 ER-positive and 39 ER-negative invasive breast cancers (71 ductal, 8 lobular) were analyzed. PR and HER2 status were recorded (34 PR-positive, 11 HER2-positive). The array was immunohistochemically stained for 8 CT antigens: MAGE-A, NY-ESO-1, GAGE, CT7, CT10, CT45, ACTL8, and NXF2. CT antigen expression was interpreted as positive when unequivocal nuclear staining was seen in any tumor cells.
Results: All CT antigens showed nuclear (CT10, CT45, ACTL8, NXF2) or mixed nuclear/cytoplasmic (MAGE-A, NY-ESO-1, GAGE, CT7) staining, with both diffuse and focal staining patterns. CT antigens showed preferential expression in hormone receptor-negative tumors; 85% of ER-negative tumors expressed at least 1 CT antigen, versus 20% of ER-positive tumors (p<0.0001). ER-negative tumors were also more likely to show simultaneous expression of >1 CT antigen than ER-positive tumors (49% vs. 5%, p<0.0001). HER2 status had less effect (p=0.19 for expression of any CT antigen), but HER2-positive tumors were more likely to express >1 CT antigen than HER2-negative tumors (73% vs. 20%, p<0.001). Among the 8 CT antigens, MAGE-A and CT7 were most frequently expressed, observed in 49% and 36% of ER-negative tumors, respectively, and 37% and 30% in the ER, PR and HER2 triple-negative subset.
Conclusions: ER-negative tumors showed significantly higher frequency of CT antigen expression, often expressing more than 1 CT antigen. HER2 status had less effect on CT expression. Our results indicate that CT-based cancer vaccine immunotherapy may potentially be useful in treating ER-negative breast cancers, including the triple-negative subset of carcinoma for which current treatment options are limited.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 64, Tuesday Morning