Loss of Caveolin 1 Expression in Breast Cancer Associated Fibroblasts Correlates with Tumor Aggressiveness
AK Witkiewicz, A Dasgupta, F Sotgia, M Sabel, CG Kleer, M Lisanti. Thomas Jefferson University, Philadelphia, PA; Kimmel Cancer Center and Thomas Jefferson University, Philadelphia, PA; University of Michigan Medical School, Ann Arbor, MI
Background: Caveolins are the principal protein components of caveolae, which are located at the cell surface . One of the caveolins, caveolin-1 (Cav-1), plays a major role in carcinogenesis through its many functions, such as gene regulation, and signal transduction. Cav-1 was reported to be downregulated during oncogenic transformation of fibroblasts. Using cell cultures established from excised breast cancers, we recently demonstrated that Cav-1 is downregulated in cancer-associated fibroblasts (CAFs), when compared to normal fibroblasts isolated from the same patient. To date, there are no studies addressing the clinical significance of stromal Cav-1 expression in invasive carcinoma of the breast. The aim of this study was to evaluate stromal Cav-1 expression in a large series of invasive breast carcinomas and to examine the association between stromal Cav-1 and clinicopathological variables.
Design: Cav-1 expression was determined by immunohistochemistry using an anti-Cav-1 antibody (Santa Cruz Biotechnology; dilution 1:100) on 160 invasive breast carcinomas, using a tissue microarray. The staining was scored semi-quantitatively as negative (0; no staining), weak (1; either diffuse weak staining or strong staining in less that 30% of stromal cells per core) and strong (2; defined as strong staining of 30% or more of the stromal cells). The median score was used for statistical analysis.
Results: Of the 160 invasive carcinomas, 147 had available cores for evaluation. Strong expression of Cav-1 in CAFs was present in 26 cases, weak in 52, and 47 cases showed an absence of Cav-1 immunostaining in CAFs (some samples could not be scored due to lack of stromal cells). There was a significant correlation of stromal Cav-1 expression with tumor grade (p=0.017) and lymph node positivity (p=0.05), with a lack of Cav-1 associated with more advanced disease. There was no association between Cav-1 and estrogen, progesterone receptors and HER2.
Conclusions: Loss of Cav-1 expression is CAFs might be a novel marker of tumor aggressiveness in breast cancers.
Monday, March 9, 2009 1:00 PM
Poster Session II # 38, Monday Afternoon