Abstract 1955: HER2 expression in African American men with prostate cancer
Authors: Mavingire Nicole Ursula , Walker Mya , Johnson Jabril R. , Sailors Isaiah J. , Ortiz-Hernandez Greisha L. , Martini Rachel N. , Davis Melissa B. , Tran Justin , Myers Frank A. , Kimbro Sean , Yin Zhirong , Dorff Tanya B. , Kittles Rick A. , Woods-Burnham Leanne 
Published: April 2023

Abstract
African American (AA) men are much more likely to be diagnosed with prostate cancer (PCa) and die from the disease than any other race/ethnicity in the United States. The pursuit of therapeutic strategies that incorporate tailored medicine for AA men remains a paramount goal. Metastatic PCa initially responds to suppression of androgen signaling through standard-of-care androgen deprivation therapy. However, relapse is inevitable, and treatment options are limited. For this reason, inhibiting androgen-independent signaling pathways that promote metastasis —such as human epidermal growth factor receptor 2 (HER2) signaling— is a promising area of investigation. HER2 overexpression in PCa tumors correlates with worse prognosis and treatment-resistance, but HER2 overexpression has not been evaluated specifically in AA men. We hypothesize that HER2 overexpression correlates with West African genetic ancestry (WAA) in AA PCa patients and worsens clinical features, treatment response, and survival outcomes. In this study, we report that HER2/ERBB2 is upregulated in the majority of PCa tumors in the Oncomine database. We quantified HER2/ERBB2 with RNAseq analysis of prostate tissue samples collected from AA patients (n=36) and observed a moderate correlation with WAA determined by genotyping using a validated set of Ancestry Informative Markers. Using immunohistochemistry, we also observed detectable HER2 protein expression in primary prostate tumors of AA patients (n=10). Our observation that 30% of AA primary tumor tissue samples were HER2-positive is remarkable, especially as previous studies have reported that HER2 overexpression is directly associated with metastasis as opposed to early, localized tumors. Our findings may underscore a basal/increased predisposition for HER2 overexpression in the AA population. We also detected HER2/ERBB2 mRNA expression using qPCR in a racially diverse panel of commonly used PCa cell lines: AA (MDA-PCa-2b and RC-77T/E) and non-Hispanic white (PC3, DU145, 22Rv1). To determine the effect of HER2 blockade on cell viability, we treated cells with 20 nM of anti-HER2 drug Trastuzumab for 72 hours and performed CellTiter-Glo™ assays. The only cell lines with significantly reduced viability were the AA cell lines. Furthermore, the RC-77T/E cell line which had the highest expression of HER2/ERBB2 also had the most significant reduction in cell viability. This finding suggests that AAs may be more responsive to HER2-targeting drugs, and that this responsiveness may be increased in PCa patients with higher levels of HER2 overexpression. It is plausible that HER2 overexpression may occur at earlier disease stages in AA men than previously reported and could be utilized to characterize aggressive PCa tumors eligible for HER2-targeting inhibitors, thus providing an early and effective therapeutic intervention that may improve outcomes in this population and reduce this appreciable health disparity.
Citation Format: Nicole Ursula Mavingire, Mya Walker, Jabril R. Johnson, Isaiah J. Sailors, Greisha L. Ortiz-Hernandez, Rachel N. Martini, Melissa B. Davis, Justin Tran, Frank A. Myers, Sean Kimbro, Zhirong Yin, Tanya B. Dorff, Rick A. Kittles, Leanne Woods-Burnham. HER2 expression in African American men with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1955.