Abstract P2-08-61: FOXA1, Nestin, GATA3 and mammaglobin expression in 164 breast cancer metastases – A retrospective immuno-histochemical study of a 10-year period (2004-2014)
Authors: J Nyqvist, S de Lara, TZ Parris, K Helou, E Kenne Sarenmalm, Z Einbeigi, P Karlsson, A Kovács
Journal: Cancer Research (2019)

Abstract Background. Including additional genes in standard immunohistochemical panels might be helpful in determining the prognosis of breast cancer patients. Pevious studies have shown that FOXA1 is a significant predictor of good outcome in breast cancer, while Nestin expression was preferentially found in triple-negative breast cancers, revealing a strong association with germline BRCA1-related breast cancer, a basal-like phenotype, stemness characteristics, high proliferation rates, p53 nuclear expression, increased rate of nodal metastases, and reduced survival (1,2,3,4). ATA3 was not only an important luminal marker, but a reliable immunohistochemical marker, which plays a crucial diagnostic role in verification of breast cancer metastases (Figure 1. and Figure 2). In a cohort containing 164 breast cancer metastases, we found GATA3 to be a reliable and sensitive diagnostic marker. We verified that the metastases originate from breast carcinoma with 95% GATA3-positivity, while mammaglobin showed only 51.2% positivity (5). According to the mammaglobin immunohistochemical prolife, we evaluated the expression of FOXA1, Nestin and GATA3 in mammaglobin-positive (n=84) and mammaglobin-negative (n=80) samples. aterials and method Full-face formalin-fixed paraffin-embedded (FFPE) specimens for 164 breast cancer metastases (from various anatomical sites) diagnosed between 2004 and 2014 were obtained from the Department of Clinical Pathology and Genetics at Sahlgrenska University Hospital (Gothenburg, Sweden). Each FFPE specimen was examined for mammaglobin, ER/PR, CK7, CK20, and HercepTest at the time of diagnosis and retrospectively analyzed for FOXA1, Nestin and GATA3 expression by immunohistochemistry (IHC). The statistical analyses were performed using a .05 P-value cutoff in R/Bioconductor (version 2.15.0) and all P-values are two-sided. The relationship between clinicopathological features and mammaglobin/GATA3 protein expression patterns was evaluated using two-tailed Fisher's exact test. Results In mammaglobin-positive metastases, FOXA1-positivity was associated with ER+ (83%) and negatively associated with triple-negativity (81%; Figure 3.). Moreover, there was no association between Nestin-positivity and the established clinicopathological features in mammaglobin-positive samples (Table 1 and Figure 4). In mammaglobin-negative samples, FOXA1-positivity was associated with GATA3+ (100%), ER+ (77%), HER2+ (36%), and triple-negative status (82% were non-triple negative). In addition, Nestin-positivity was associated with specific metastatic sites (mostly brain, but even gynecological sites and skin), GATA3- (29%), ER- (50%), PR- (79%), and triple-negative status (50% were triple negative) in mammaglobin-negative samples (Table 2). Conclusion In the present study, we found that FOXA1 was expressed mostly in ER-positive breast cancer metastases and Nestin expression was associated with breast cancer metastases with a triple-negative immune profile, where the brain was the most frequent metastatic site. Citation Format: Nyqvist J, de Lara S, Parris TZ, Helou K, Kenne Sarenmalm E, Einbeigi Z, Karlsson P, Kovács A. FOXA1, Nestin, GATA3 and mammaglobin expression in 164 breast cancer metastases – A retrospective immuno-histochemical study of a 10-year period (2004-2014) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-61.