Loss of Stromal Caveolin-1 Independently Predicts Poor Disease-Free Survival and Time to Recurrence in Patients with Prostate Cancer
M Wagner, A Dasgupta, F Sotgia, RB West, MP Lisanti, AK Witkiewicz. Thomas Jefferson University, Philadelphia, PA; Kimmel Cancer Center; Thomas Jefferson University, Philadelphia, PA; Stanford University Medical Center, Stanford, CA
Background: In recent years it has become evident that stromal cell and extracellular matrix interact with tumor epithelium to influence cancer progression. Fibroblasts isolated from tumor stroma termed “cancer associated fibroblasts” show an ability to prevent cancer cell apoptosis, induce cancer cell proliferation, and stimulate tumor angiogenesis. Downregulation of the protein caveolin-1 (Cav-1) is one of the mechanisms implicated in the oncogenic transformation of fibroblasts. Recently we demonstrated that loss of stromal Cav-1 expression was associated with poor clinical outcome in breast cancer patients. In this study we sought to correlate tumor stromal Cav-1 expression with clinical outcome in prostate cancer patients.
Design: A tissue microarray (TMA) was constructed using tissue core samples from 167 human prostate cancers of varying stages and Gleason grades. Cav-1 expression was assessed in both epithelium and stroma using a standard immuno-peroxidase method (rabbit polyclonal pan-Cav Ab, BD Biosciences, 1:1000 dilution). The staining was scored semi-quantitatively as negative (0), equivocal (1), weak positive (2), or strong positive (3). Scores of 0-2 were considered indicative of loss of Cav-1 expression. Statistical analysis of the association of Cav-1 expression and the usual markers of disease severity was performed using the Fisher exact test or the Kruskal-Wallis test. Kaplain-Meier survival curves were also generated.
Results: Statistical analysis revealed no significant association between stromal Cav-1 loss and the usual markers of disease severity including Gleason grade, stage and presence of metastases. Kaplan-Meier survival curves showed a significant association between stromal Cav-1 loss and poor disease-free survival and time to recurrence (p<0.05), but no significant association with cancer-specific survival.
Conclusions: We found that loss of stromal Cav-1 in human prostate cancers predicts poor disease-free survival and time to recurrence. We found no significant association between Cav-1 loss and the usual makers of disease severity and therefore conclude that loss of stromal Cav-1 is an independent factor in predicting poor clinical outcome. Since loss of Cav-1 is not prognostic of poor cancer-specific survival, the outcome may be affected through the recurrence rate.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 110, Wednesday Afternoon