Abstract LB-320: Expression of NY-ESO-1, MAGE-A3, PRAME and WT1 in different subgroups of breast cancer.
Authors: Tessari Anna , Pilla Lorenzo , Paolini Biagio , Carcangiu Maria Luisa , Mariani Luigi , Moliterni Angela , Braud Filippo De , Cresta Sara 
Published: August 2014

Background:

Melanoma studies have highlighted the existence of tumor-specific antigens highly immunogenic, to whom a strong immune response can be induced. This was the starting point to investigate the expression of Cancer Testis Antigens (CTa) in Breast Cancer (BC), with the objective to define if highly aggressive tumors have a different antigenic panel. Among the most immunogenic and tumor-specific CTa, we have selected NY-ESO-1, MAGE-A3 and PRAME, in addition to WT1.

Materials and Methods:

4 subgroups numerically homogeneous of BC patients who underwent surgery consecutively from 2003 at our Institution, were selected by the expression of ER, PgR and Her2 (IHC 3+): Group 1 ER+ any PgR or Her2 (22 evaluable patients), Group 2 ER- PgR+ any Her2 (15), Group 3 ER- PgR- Her2+ (24), Group 4 ER- PgR- Her2- (TNBC, 18). Tissue microarray (TMA) was performed on a total of 99 Invasive BC (83 evaluable). From representative paraffin-embedded block, we obtained 3 tissue-cores of 1.5 mm diameter that were used for TMA construction. Sections were stained for NY-ESO-1, MAGE-A3, PRAME and WT1.

Results:

NY-ESO-1 was the only differentially expressed antigen among BC subgroups (p=0.0068).

In our series, none ER+ case expressed NY-ESO-1. NY-ESO-1 expression rate was 0% also in ER- PgR+ tumors. This data could mean an exclusive expression of either NY-ESO-1 or at least one hormonal receptor (HR+) (p=0.0016).

In line with published results, NY-ESO-1 was expressed in a share of HR- tumors, and it was particularly represented in TNBC (28.6% vs 16% of Her2+).

From the immunoistochemical analysis of MAGE-A3 and PRAME, there did not seem to be a correlation between their expression and the receptor status of the tumor. Each subgroup had high positivity for both of them (MAGE-A3 range 86.4-100%, PRAME range 81.3-100%).

In our case study, WT1 had low expression (range 0-6.3%), except for the Her2+ group (16%).

The biological characteristics of the NY-ESO-1 expressing subgroups were analyzed.

In ER-PgR-Her2+ tumors, the expression of NY-ESO-1 was related to: high grade (100% G2-G3), T≥2cm (100%) and nodal involvement (100%). In TNBC, the expression of NY-ESO-1 seemed to be associated to an earlier stage of disease and to a less aggressive biological behavior. The rate of T≥2cm tumors was 60%; 60% of cases were node negative. Due to the small sample size, this association was not statistically significant.

Conclusions:

This study defines a distinction between HR+ and HR- tumors through NY-ESO-1 expression. TNBC is the subgroup with the highest frequency of NY-ESO-1+ cases.

NY-ESO-1 positivity seems to be associated with higher aggressiveness in ER-PgR-Her2+ patients. Conversely, NY-ESO-1 positivity appears to correlate with a less aggressive biological behavior in TNBC group.

This study defines the TNBC as the ideal subgroup for the development of an anti-NY-ESO-1 vaccine, suggesting the hypothesis of a better applicability in the early stage of disease.

Citation Format: Anna Tessari, Lorenzo Pilla, Biagio Paolini, Maria Luisa Carcangiu, Luigi Mariani, Angela Moliterni, Filippo De Braud, Sara Cresta. Expression of NY-ESO-1, MAGE-A3, PRAME and WT1 in different subgroups of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-320. doi:10.1158/1538-7445.AM2013-LB-320