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

Breast. 2018 Dec:42:68-73. doi: 10.1016/j.breast.2018.08.106. Epub 2018 Aug 29.

Abstract

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.

Keywords: Breast cancer; Immunotherapy; MAGE-A3; NY-ESO-1; PRAME; Tumor antigens; Vaccine; WT1.

MeSH terms

  • Adult
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / therapy
  • Cohort Studies
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Melanoma-Specific Antigens / metabolism*
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • WT1 Proteins / metabolism*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CTAG1B protein, human
  • MAGEA1 protein, human
  • MAGEA3 protein, human
  • Melanoma-Specific Antigens
  • Membrane Proteins
  • Neoplasm Proteins
  • WT1 Proteins
  • WT1 protein, human