Expression of MAGE-A and NY-ESO-1 cancer/testis antigens is enriched in triple-negative invasive breast cancers

Abstract

Aims: A better understanding of the expression of cancer/testis antigens (CTAs) in breast cancer might enable the identification of new immunotherapy options, especially for triple-negative (TN) tumours, which lack expression of the conventional therapeutic targets oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The aim of this study was to quantify the expression of MAGE-A and NY-ESO-1 CTAs in breast cancer, and relate this to known clinicopathological parameters. Methods and results: We surveyed MAGE-A and NY-ESO-1 expression in an unselected cohort of 367 breast tumours (of which 65 were TN), with accompanying clinical follow-up data, by using immunohistochemical analysis of tissue microarrays. Relevant to their potential as vaccine targets in breast cancer, MAGE-A was expressed in 13% of cases, and NY-ESO-1 in 3.8%, with the majority of tumours showing fairly homogeneous staining within individual tissue cores (~85% of cases with staining in >75% of tumour cells). Most NY-ESO-1-positive cases also expressed MAGE-A (P = 2.06 × 10−9), and both were strongly associated with the TN phenotype (P < 0.0001), with the most proliferative and poorly differentiated cases, in paticular, showing genomic instability. This was characterised by coexpression of c-Kit and TTK, and overexpression of p53. Conclusions: MAGE-A and NY-ESO-1 are frequently expressed in TN breast cancer (~47% and 17% of TN cases, respectively), suggesting that targeting them could be feasible in this patient group. Expression is reasonably homogeneous in positive cases, suggesting that immunohistochemical analysis of tissue biopsies would be a reliable companion biomarker.