An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers

Agnieszka K. Witkiewicz, Abhijit Dasgupta, Federica Sotgia, Isabelle Mercier, Richard G. Pestell, Michael Sabel, Celina G. Kleer, Jonathan R. Brody, Michael P. Lisanti

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224 Scopus citations

Abstract

Previously, we showed that caveolin-1 (Cav-1) expression is down-regulated in human breast cancer-associated fibroblasts. However, it remains unknown whether loss of Cav-1 occurs in the breast tumor stroma in vivo. Here, we immunostained a well-annotated breast cancer tissue microarray with antibodies against Cav-1 and scored its stromal expression. An absence of stromal Cav-1 was associated with early disease recurrence, advanced tumor stage, and lymph node metastasis, resulting in a 3.6-fold reduction in progression-free survival. When tamoxifen-treated patients were selected, an absence of stromal Cav-1 was a strong predictor of poor clinical outcome, suggestive of tamoxifen resistance. Interestingly, in lymph node-positive patients, an absence of stromal Cav-1 predicted an 11.5-fold reduction in 5-year progression-free survival. Clinical outcomes among patients positive for HER2, and patients triple-negative for estrogen receptor, progesterone receptor and HER2, were also strictly dependent on stromal Cav-1 levels. When our results were adjusted for tumor and nodal staging, an absence of stromal Cav-1 remained an independent predictor of poor outcome. Thus, stromal Cav-1 expression can be used to stratify human breast cancer patients into low-risk and high-risk groups, and to predict their risk of early disease recurrence at diagnosis. Based on related mechanistic studies, we suggest that breast cancer patients lacking stromal Cav-1 might benefit from anti-angiogenic therapy in addition to standard regimens. We conclude that Cav-1 functions as a tumor suppressor in the stromal microenvironment.

Original languageEnglish (US)
Pages (from-to)2023-2034
Number of pages12
JournalAmerican Journal of Pathology
Volume174
Issue number6
DOIs
Publication statusPublished - Jun 2009

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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