Abstract P3-10-23: Caveolin 1 and Patient Outcomes in Breast Cancer
Authors: Bambury RM , Gonzalez-Angulo A-M , Carey MS , Sahin A , Brown P , Speers C , Lluch A , Mills GB , Hennessy BT 
Published: April 2011

Introduction: Caveolin 1 (Cav1) protein is a structural component of caveolae in cell membranes and is also present in the cell cytoplasm, nucleus and extracellular milieu. It regulates multiple cellular processes and has been reported to both positively and negatively effect tumour progression. In normal and malignant breast tissue Cav1 is immunohistochemically expressed in myoepithelial and stromal cells but rarely in luminal epithelial or breast cancer cells. Recent reports have correlated Cav1 expression in the stromal tumour microenvironment with lower tumor stage, grade and improved prognosis. This suggests a separate role for Cav 1 in influencing tumour behaviour by regulating the tumour microenvironment. Our aim was to further investigate the role of Cav1 in breast cancer by for the first time analysing its expression by reverse phase protein array(RPPA). Methods: We examined expression levels of Cav1 in 52 breast cancer cell lines and a large human early breast cancer cohort(n=712) with cancer cells composing 70% of the macrodissected breast cancer specimens used. Data was recorded when available for each case on standard clinical, pathological and survival endpoints. We examined the effect of Cav1 expression on tumour biology and patient survival. Results: High levels of Cav1 expression in breast cancer cell lines was strongly correlated with a TN phenotype (P&lt;0.001). Cav 1 expression was more strongly associated with the stromal subtype rather than basal subtype of TN cell lines (p=0.02).

In contrast, in human tumour tissue high levels of Cav1 correlated with the hormone receptor positive(ER) phenotype. There was also an association between Cav 1 expression and lower grade (P&lt;0.001), lower T stage (P&lt;0.001) and lower N stage (P&lt;0.001).

Cav 1 was significantly associated with improved relapse-free (RFS) and overall survival (OS) in the human cohort. On multivariate(MV) analysis Cav1 was associated with OS(HR 0.91/95% CI 0.82-1/p=0.05) but not RFS. In the subset of ER patients who only received adjuvant tamoxifen (n=199) Cav1 was also significantly associated with improved RFS and OS. MV analysis again showed this correlation to remain for OS (HR 0.81/95% CI 0.65-1/p=0.05) but not for RFS. In the TN subset (n=161) Cav1 expression did not have any survival impact. Discussion: Our results show different expression patterns of Cav1 in vitro and in vivo. TN tumors are thought to originate from the myoepithelial or stromal component of breast tissue which may explain the high levels of Cav1 in this subgroup of breast cancer cell lines. On the other hand, human tumour tissue showed an association between high Cav1 levels and ER tumours. Analysis of these macrodissected samples likely included stromal tissue surrounding the epithelial tumour cells which may explain this discrepancy.

Our data also show a correlation between high in vivo levels of Cav1 and less aggressive tumours with improved prognosis. On MV analysis Cav1 was an independent predictor of outcome in the whole cohort and in the ER subset treated with adjuvant tamoxifen only. Expression of stromal Cav1 measured by RPPA may again partly explain these findings. Further analysis with fully microdissected human breast tissue and immunohistochemical analysis of both stromal and cancer cell Cav1 expression is planned.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-23.