Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 174, Issue 6, Pages 2023-2034Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2009.080873
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Funding
- NIH/NCI [R01-CA-80250, R01-CA-098779, R01-CA-120876, R01-CA-090876, R01-CA107469, R01-CA-70896, R01-CA-75503, R01-CA-86072, R01-CA-107382, P30-CA-56036]
- American Association for Cancer Research
- Department of Defense-Breast Cancer Research Program (Synergistic Idea Award)
- Susan G. Komen Career Catalyst Grant
- Breast Cancer Alliance, Inc.
- Elsa U. Pardee Foundation
- W.W. Smith Charitable Trust
- American Cancer Society
- Avon Foundation
- Pennsylvania Department of Health
- Dr. Ralph and Marian C. Falk Medical Research Trust
- NATIONAL CANCER INSTITUTE [R01CA107382, R01CA120876, K08CA090876, R01CA098779, P30CA056036, R01CA107469, R01CA070896, R01CA075503, R01CA086072, R01CA080250] Funding Source: NIH RePORTER
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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. (Am J Pathol 2009, 174:2023-2034; DOI:10.2353/ajpath.2009.080873)
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