P1-03-09: Significance of FAP, SMA and CD31 Expression in the Stroma of Breast Cancer.

Abstract

Abstract Breast cancer stroma heterogeneity has been demonstrated in various gene expression profile analyses. Whether there is any association between stroma heterogeneity and the molecular phenotype of breast cancer has yet to be established. Therefore, we performed immunohistochemical analyses (IHC) to evaluate the expression of the following stromal cell markers (fibroblast activation protein (FAP), smooth muscle actin (SMA), and CD31, an endothelial cell marker) in tumor tissues from a contemporary cohort of 52 patients comprising of all four molecular subtypes (luminal A (n=25); luminal B (n=2); Her2-neu (+) (n=5); and basal (n=20)). We hypothesize that stroma heterogeneity as reflected by the proportion of stromal cells staining (+) for FAP and SMA may correlate with their molecular epithelial phenotype. Furthermore, studying the distribution of these stromal cell markers in IHC sections may evaluate their spatial relationship with tumor cells, immune cells, and tumor microvasculature which may have strategic significance within the tumor/microenvironment. As shown in Table 1, FAP is a more robust stromal cell marker staining 85±14% of stromal cells compared to SMA which stains only 28±29% of stromal cells (p<0.05). However, the distribution of FAP, SMA and microvessel density appears to be similar in all four subtypes. Multivariate analyses to correlate molecular subtype, tumor grade, tumor size, the no. of (+) nodes, and age with the% stromal cells staining (+) for FAP, SMA and CD31 yielded a significant correlation between the intensity of FAP(+) cells with tumor size, tumor grade, and the no. of positive nodes (p=0.00134, 0.0044, and 0.01141 respectively). We conclude that 1) stroma heterogeneity on IHC does not differ significantly across molecular subtypes; 2) FAP is a robust stromal cell marker; and 3) a higher FAP expression intensity on IHC may correlate with poor prognosis. Recent reports on the role of FAP in promoting tumor growth plus the abundance of FAP expression in breast cancer stroma underscore a significant role of FAP in breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-03-09.