Abstract P3-10-40: Expression and Prognostic Significance of Cancer Testis Antigens (CTA) in Primary Breast Cancer: Possible Diagnostic Markers and Therapeutical Targets

Abstract

Abstract Backround: Cancer Testis Antigens (CTA) are a family of proteins normally expressed in the human germ cells such as in the testis. They also have been found in various types of malignant tumors including breast cancer. Because of their restricted expression pattern they are frequently able to elicit T-cell immune responses, and therefore they are considered as ideal targets for cancer immunotherapy. Breast differentiation antigen NY-BR-1 has also immunogenic properties. The aim of this study was to explore the CTA expression in breast cancer and detect possible clinical correlations. Materials and Methods: The expression patterns of 6 CTAs (MAGE A1- MA454, MAGE A3-M3H67, MAGE A4-57B, NY-ESO-1-E978, GAGE, MAGE A-6C1) and NY-BR-1 were examined by immunohistochemistry in a series of 210 non-selected patients with primary invasive breast cancer using the tissue microarray technique. The intensity of the stain was scored semi-quantitatively in a scale 0 to+3. The expression of the antigens was correlated to established clinicopathological parameters as well as disease-free (DFS) and overall (OS) survival. Results: CTA expression exhibited a predominantly cytoplasmic and occasionally nuclear localization. At least one CTA was identified in 37.2% of cases with expression of each antigen varying from 4.5 to 15%. NY-BR-1 was positive in 46.6% of tumors, with the well differentiated tumors showing more frequent expression. MAGE A4-57B (p=0.028 and 0.015) and MAGE A3-M3H67 (p=0.001 and 0.004, respectively) positivestaining was significantly correlated to shorter OS and DFS. MAGE A1-MA454 correlated significantly only with OS (p=0.028). GAGE and MAGE A-6C1 displayed a clear trend, but not statistically significant prognostic value concerning shorter DFS and OS. In multivariate analysis only MAGE A3-M3H67 (p=0.007 OS) and MAGE A4-57B (p=0.017 DFS, 0.052 OS) showed and independent prognostic relevance. Additionally, the mortality rate increased substantially if co-expression of any 3 or more CTAs was observed. Discussion: Our findings suggest that CTAs could serve as potential prognostic markers in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define potential new targets for specific breast cancer therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-40.