Abstract B04: Epithelial nuclear androgen receptor (AR) in radical prostatectomy samples as assessed by quantitative immunofluorescence is differentially expressed in African American versus Caucasian cases
Authors: McBride Russell Bailey , Khan Faisal M. , Rybicki Benjamin A. , Cordon-Cardo Russell 
Published: October 2015

Introduction: Numerous biomarkers are being evaluated as potential predictors of prostate cancer (PCa) recurrence after definitive surgical treatment with radical prostatectomy (RP). In particular, there is a significant literature on the importance of androgen receptor (AR) protein expression in predicting the aggressiveness of PCa as well as the probability of response to secondary therapeutic interventions (e.g. androgen deprivation therapy. The AR axis has been a primary target for researchers seeking treatment options for patients whose prostate cancer is not cured by surgery alone. By utilizing quantitative immunofluorescence (IF) multiplexed biomarkers assessd via spectral imaging, we evaluated whether AR expression is deferentially expressed by race.

Methods: We performed multiplex immunoflorescence immunohistochemistry on tissue microarrays (TMA) made from representative cores of tumor tissue from formalin-fixed, paraffin-embedded prostatectomy samples from cases treated for PCa by RP at the Henry Ford Health System between 2001 and 2005. There were 400 stained cores sampled from 149 African American (AA) cases and 453 cores from 195 Caucasian American (CM) cases. The samples were stained by a multiplex IF assay which contained the nuclear marker DAPI, along with AR and CK18. The co-localization of DAPI, CK18 and AR permitted quantitative analysis of AR expression in only the epithelial nuclei, a known cellular compartment of prognostic expression. Differences in expression were evaluated using the Wilcoxon rank sum test. The association between race and AR expression level was adjusted for potential confounding covariates using non-parametric generalized additive models.

Results: There was a statistically significant difference in the expression of AR signal in epithelial nuclei between Caucasian men and African American men, p-value = 0.03. The association between Race and AR remained statistically significant (p=0.02) even after adjusting for established clinical risk factors of PCa (age, grade, stage and PSA). It is also noteworthy that there were no statistically significant differences in age, grade, stage or PSA when comparing Caucasian and African American men in our dataset.

Conclusions: AR levels in RP epithelial nuclei have previously been found to be a useful tool in guiding therapeutic response for men who have failed surgical therapy for their prostate cancer. However, our results suggest that even with other clinical risk factors being equal, such molecular metrics may be different across racial subgroups of patients. It is possible that expression of these molecular features may be affected by external exposures, or genetic factors which differ by race, but are not necessarily related to the underlying disease mechanisms we seek to measure. Additional research into such differences is necessary as the African American community would benefit from the development of molecular diagnostic assays specifically tailored to this population. Current practices in biomarker discovery rarely address the possibility of racial variation, thereby leading to a potentially inaccurate or incorrect assessment of disease severity and consequent therapy for African American PCa patients.

Citation Format: Russell Bailey McBride, Faisal M. Khan, Benjamin A. Rybicki, Russell Cordon-Cardo. Epithelial nuclear androgen receptor (AR) in radical prostatectomy samples as assessed by quantitative immunofluorescence is differentially expressed in African American versus Caucasian cases. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B04.