Multiple Cancer/Testis Antigens Are Preferentially Expressed in Hormone-Receptor Negative and High-Grade Breast Cancers

Abstract

BackgroundCancer/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 FindingsIn 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/SignificanceCT 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.

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

“…The results showed that MAGE-A was specifically expressed in neoplastic samples with a percentage of 49.17%. Chen et al [37] showed 17% of MAGE-A-positive cases and Kavalar et al [38] observed 64.2% of MAGE-A -expressed cases. The differences may be due to the diverse primary antibodies and scoring methods we used.…”

“…Also, MAGE-A-positive cases were often with high histological grade and metastatic axillary lymph nodes, which strengthened the association between MAGE-A and cancer progression. According to some studies, MAGE-A proteins have to do with negative hormone receptor status, high histologic grade [37,39], large tumor size (≥2cm) [36], positive sentinel lymph nodes (SLN) [40], high Ki-67 score [27] and HER-2 negativity. Notably, MAGE-A expression is contributed to unfavorable outcomes and cancer development.…”

Cancer–Testis Antigen Expression in Digestive Tract Carcinomas: Frequent Expression in Esophageal Squamous Cell Carcinoma and Its Precursor Lesions

“…In urothelial carcinoma, expression of MAGEA and NY-ESO-1 was more often found in high-grade carcinomas in comparison with low-grade cancers (19,20). In breast carcinoma, the expression of multiple CT-X antigens was more frequent in hormone-receptor-negative carcinomas and in tumors greater than 2 cm in size (21,22).…”

Cancer‑testis antigens are predominantly expressed in uterine leiomyosarcoma compared with non‑uterine leiomyosarcoma

“…NY-ESO-1 expression was detected in invasive ductal carcinoma of the breast (11.2%) (27), metastatic malignant melanoma (32.0%) (28), head and neck squamous cell carcinoma (4.3%) (29) and non-small cell lung cancer (25.0%) (30). GAGE7 expression was detected in spermatocytic seminoma (67.0%), seminomas (4.0%) (31) and advanced breast carcinoma (43.9%) (32).…”