Advances in Brief Elevated Caveolin-1 Levels in African-American versus White- American Prostate Cancer 1 Guang Yang, Josephine Addai, Michael Ittmann, Thomas M. Wheeler, and Timothy C. Thompson 2 Departments of Urology [G. Y., J. A., T. M. W., T. C. T.], Pathology [M. I., T. M. W.], Molecular and Cellular Biology [T. C. T.], and Radiology [T. C. T.], Baylor College of Medicine, Houston, Texas 77030 Abstract Clinical studies suggest that African-American (AA) prostate cancer patients manifest a more aggressive form of the disease compared with white prostate cancer patients. However, the biological underpinnings of this potential dif- ference remain unresolved. To address this issue, we used specific quantitative immunostaining protocols to determine whether a panel of biomarkers related to apoptosis includ- ing caveolin-1, bcl-2, p53, and c-myc were differentially expressed in AA versus white prostate cancer patients with similar clinical and pathological characteristics. We further attempted to correlate biomarker positivity with prolifera- tion-related markers including Ki-67 labeling index and apoptotic index. Interestingly, our results indicated that only the incidence of caveolin-1 staining was significantly differ- ent between these two ethnic/racial groups of prostate can- cer patients. The incidence of caveolin-1 staining in white patients was 17% compared with 39% in AA patients (P  0.0048; Fisher’s exact test). In addition, the percentage of caveolin-1-positive prostate cancer cells was also higher in moderately differentiated (Gleason score 6) prostate cancer patients in AA versus whites. Because caveolin-1 has been shown previously to demonstrate antiapoptotic activities in prostate cancer cells, our results suggest that differences in caveolin-1 expression may in part underlie the apparent differences in the clinical virulence of this disease in AA versus white prostate cancer patients. Introduction Both the age-adjusted incidence and mortality rates of prostate cancer in AA 3 men have been reported to be signifi- cantly higher than those in white-American men (1, 2). Socio- economic factors may partially explain these differences be- cause at diagnosis AA tend to have higher clinical stage (3) and more poorly differentiated cancer (4). However, AA patients who have equal excess to medical service and have similar pathological stage at diagnosis as their white counterparts still have significantly higher rates of recurrence after radical pros- tatectomy and increased overall death rate from this disease (5, 6). Overall, the clinical data suggest that intrinsic differences in the biological activity of the cancer per se and/or the host response to it underlie the more virulent nature of AA versus white prostate cancer. Thus far, studies designed to identify discriminating biomarkers in AA versus white patients that may predispose toward or contribute to more aggressive AA prostate cancer have been limited and in general inconclusive (reviewed in Refs. 7–9). We have identified previously caveolin-1 expres- sion as being up-regulated in metastatic prostate cancer (10) and as a biomarker that has independent prognostic value in recur- rent prostate cancer after radical prostatectomy (11). We have further shown that caveolin-1 can promote survival through antiapoptotic activities in prostate cancer cells in vitro and in vivo under adverse conditions, such as withdrawal of testoster- one (12). In this study, we used specific immunostaining pro- tocols to determine whether caveolin-1 or other biomarkers including bcl-2, p53, and c-myc are differentially expressed in AA versus white prostate cancer. We further attempted to cor- relate biomarker positivity with proliferation-related markers, i.e., KiI (percentage of Ki67-positive cancer cells) and AI (num- ber of apoptotic cells per 1000 cancer cells). Materials and Methods Patients and Prostate Specimens. Prostate cancer spec- imens from 71 AA and 71 white (non-Hispanic) men that had clinically confined cancers and had undergone radical prosta- tectomy were obtained. None of these patients had previously received neoadjuvant hormone therapy. This set of specimens was matched for pathological stage by a statistician such that each group had 49 patients with organ-confined disease, 14 with extraprostatic invasion only and 8 with seminal vesicle invasion, and their cancers had similar average Gleason scores (6.35 for the AA and 6.46 for the whites). The two groups of patients also had comparable average ages (62.00 for the AA and 62.14 for the whites) and preoperative prostate-specific antigen levels (9.2  6.8, mean  SD, in AA and 8.2  5.2 in the whites). Statistical comparisons in pathological stage, Gleason score, and Received 2/11/00; revised 6/26/00; accepted 6/29/00. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 This work was supported by Grants CA50588, CA68814, and Spe- cialized Programs of Research Excellence P50-58204 from the National Cancer Institute. 2 To whom requests for reprints should be addressed, at Scott Depart- ment of Urology, Baylor College of Medicine, 6560 Fannin, Suite 2100, Houston, TX 77030. Phone: (713) 799-8718; Fax: (713) 799-8712; E- mail: timothyt@bcm.tmc.edu. 3 The abbreviations used are: AA, African American(s); KiI, Ki67 labeling index; AI, apoptotic index. 3430 Vol. 6, 3430 –3433, September 2000 Clinical Cancer Research