Abstract 4266: Identification of gene expression profiles associated with different types of breast adipose and their relationship to tumorigenesis

Abstract

Abstract Background: Research over the past decade has shown the importance of the stroma in tumorigenesis, however, having long been thought to function only as an inert energy storage depot, the role of adipose tissue in tumorigenesis has been largely ignored. Improved understanding of the role of adipose in tumorigenesis is crucial given the increasing rates of obesity and the use of autologous fat transfer in breast reconstruction. Methods: Adipose, adjacent to and distant from invasive breast tumors, was laser microdissected from 20 post-menopausal women, and from 20 post-menopausal women with non-malignant breast disease. Gene expression data were generated using U133 2.0 microarrays. After quality control and visualization steps, the data were analyzed to identify significant patterns of differential expression between adipose classes, at the individual gene and molecular pathway level. Results: Pathway analysis revealed that immune response differs between non-malignant, distant and tumor adjacent adipose; this response is seen as a gradient with the largest response closest to the tumor. Gene expression differed significantly in adipose from invasive compared to non-malignant breasts with FCGR2A, FOLR2, LGMN, MARCO and NLRP3 expressed at significantly higher levels and HLA-DQB1 and HLA-DQA1 at significantly lower levels in adipose from invasive breasts. Within the invasive breasts, MMP9, PLA2G7, RRM2 and SPP1 were expressed at >3-fold higher levels in adjacent compared to distant adipose. Conclusions: Gene expression levels differ in breast adipose, depending on presence of or proximity to tumor cells. Adipose adjacent to the tumor demonstrated the largest immune response; this response may reflect a reaction to surgical insult from the original biopsy; however, response to surgical injury has been associated with increased ability to metastasize. In addition, within breasts with invasive breast cancer, genes involved in cellular proliferation, degradation of the extracellular matrix and angiogenesis were expressed at higher levels in adjacent compared to distant adipose. Together, these data suggest that adipose is not an inert component of the breast microenvironment but plays an active role in tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4266. doi:1538-7445.AM2012-4266