Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers

• Published in: Cancer biology & therapy 2010-07, Vol.10 (2), p.135-143
• Main Authors: Witkiewicz, Agnieszka K., Dasgupta, Abhijit, Sammons, Sara, Er, Ozlem, Potoczek, Magdalena, Guiles, Fran, Sotgia, Federica, Brody, Jonathan R., Mitchell, Edith P., Lisanti, Michael P.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Binding; Biology; Biomarkers, Tumor - metabolism; Bioscience; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Calcium; Cancer; Caveolin 1 - metabolism; Cell; Cohort Studies; Connective Tissue - metabolism; Cycle; Epithelium - metabolism; ErbB Receptors - metabolism; Female; Humans; Kaplan-Meier Estimate; Keratin-5 - metabolism; Keratin-6 - metabolism; Landes; Middle Aged; Organogenesis; Predictive Value of Tests; Prognosis; Proteins; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - analysis; Research Paper; Statistics, Nonparametric; Survival Analysis
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.10.2.11983

Here, we investigated the possible predictive value of stromal caveolin-1 (Cav-1) as a candidate biomarker for clinical outcome in triple negative (TN) breast cancer patients. A cohort of 85 TN breast cancer patients was available, with the necessary annotation and nearly 12 years of follow-up data. Our primary outcome of interest in this study was overall survival. Interestingly, TN patients with high-levels of stromal Cav-1, had a good clinical outcome, with >50% of the patients remaining alive during the follow-up period. In contrast, the median survival for TN patients with moderate stromal Cav-1 staining was 33.5 months.  Similarly, the median survival for TN patients with absent stromal Cav-1 staining was 25.7 months. A comparison of 5-year survival rates yields a similar pattern. TN patients with high stromal Cav-1 had a good 5-year survival rate, with 75.5% of the patients remaining alive. In contrast, TN patients with moderate or absent stromal Cav-1 levels had progressively worse 5-year survival rates, with 40% and 9.4% of the patients remaining alive.  In contrast, in a parallel analysis, the levels of tumor epithelial Cav-1 had no prognostic significance. As such, the prognostic value of Cav-1 immunostaining in TN breast cancer patients is compartment-specific, and selective for an absence of Cav-1 staining in the stromal fibroblast compartment. A recursive-partitioning algorithm was used to assess which factors are most predictive of overall survival in TN breast cancer patients. In this analysis, we included tumor size, histologic grade, whether the patient received surgery, radiotherapy or chemotherapy, CK5/6, EGFR, p53 and Ki67 status, as well as the stromal Cav-1 score. This analysis indicated that stromal Cav-1 expression was the most important prognostic factor for overall survival in TN breast cancer. Virtually identical results were obtained with CK5/6 (+) and/or EGFR (+) TN breast cancer cases, demonstrating that a loss of stromal Cav-1 is also a strong prognostic factor for basal-like breast cancers.  Our current findings may have important implications for the close monitoring and treatment stratification of TN and basal-like breast cancer patients.