Expression of NY-ESO-1, MAGE-A3, PRAME and WT1 in different subgroups of breast cancer : an indication to immunotherapy?

Objectives: Cancer Testis Antigens are immunogenic tumor-specific proteins. We investigated NY-ESO-1, MAGE-A3 and PRAME, in addition to WT1 expression in different Breast Cancer (BC) subtypes. We then evaluated the expression rate of NY-ESO-1 in early Triple Negative breast cancer (TNBC), and investigated whether its expression would be maintained or lost in the metastatic setting to explore possible immunotherapy indication. Materials and methods: Three subgroups of BC patients were selected by the expression of ER, PgR and Her2. Tissue microarray was performed on a total of 92 Invasive BC. Sections were stained for NY-ESO-1, MAGE-A3, PRAME and WT1. The second cohort was composed by 26 metastatic TNBC patients from whom both the primary and secondary lesion tissues were available. Sections were stained for NY-ESO-1. Results: NY-ESO-1 was the only differentially expressed antigen and was absent in ER+ and ER-PgR + tumors, as for an exclusive expression of either NY-ESO-1 or at least one hormonal receptor (HR+). NY-ESO-1 was particularly represented in TNBC. No correlation has been found between MAGE-A3 and PRAME expression and subtype WT1 had low expression, except in the Her2+ group. In the second cohort, NY-ESO-1 was expressed in 12 and 24% of primary and metastatic lesions respectively. Conclusions: This study defines a distinction between HR+ and HR-tumors through NY-ESO-1 expression. TNBC subgroup has the highest frequency of NY-ESO-1+ cases, and it could be the candidate population for the development of anti-NY-ESO-1 vaccine, both in the adjuvant or metastatic setting, and for the selection of cases suitable for immunotherapy. Precis: NY-ESO-1 is the only differentially expressed antigen between breast cancer subgroups, among those we evaluated, and is restricted to hormonal receptors negative cases with the highest frequency in Triple Negative breast cancer, thus indicating its possible role as anticancer vaccine target in a poor prognosis subgroup still lacking of specific therapies.