Abstract 5563: Androgen receptor (AR) is frequently found in human cancers and inversely linked to patient outcome in breast and renal cell carcinomas

Abstract

Abstract Background: Androgen receptor (AR) is a nuclear transcription regulator which mediates the growths stimulating effect of androgens. Inhibition of AR signaling is the most important first line therapy in prostate cancer. Clinical trials are ongoing for molecularly defined subsets of breast cancers expressing AR. In surgical pathology, AR immunohistochemistry is used as a marker for prostate cancer. Design: To comprehensively determine AR expression in normal and neoplastic tissues, a tissue microarray containing 18,234 samples from 141 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: AR positivity was found in 116 of 141 tumor categories, and 66 of these tumor categories contained at least one case with strong AR staining. AR positivity was most seen in different categories of prostate cancer (87.8-100%), various subtypes of breast cancer (34.3-94.9%) and ovarian cancers (48.7-97.1%), in endometrial cancers (53-61.1%), salivary duct carcinomas (70%), teratomas (60%), renal cell carcinomas (41.8-62.7%), urinary bladder cancers (43.2-48.7%), granular cell tumors (40.7%), leiomyosarcomas (33.3%), gastrointestinal stroma tumors (31.1%) and urothelial carcinomas of the kidney pelvis (30.4%). Seventy-seven additional tumor types showed AR expression in up to 30% of the analyzed samples, but AR expression was typically only weak in these tumors. Among 1,430 evaluable invasive breast carcinomas of no special type (NST), absent or low AR immunostaining was significantly linked to high BRE grade (p<0.0001), advanced pT stage (p<0.0001), presence of nodal and distant metastasis (p<0.0001 each), HER2 overexpression (p=0.005), reduced estrogen and progesterone receptor expression (p<0.0001 each), triple negative status (p<0.0001) and shortened patient survival (p=0.0024). Among 1,149 clear cell renal cell cancers (RCC), low AR immunostaining was linked to high ISUP, Fuhrman and Thoenes grades (p<0.0001 each), high UICC and pT stage (p<0.0001 each), presence of distant metastases (p=0.0075), and reduced time to recurrence (p=0.0007), overall survival (p=0.0097) and tumor-specific survival (p=0.0129). In 297 papillary RCC, low AR staining was associated with high ISUP grade (p=0.0179), advanced pT stage (p=0.0055) and nodal metastasis (p=0.0044). Low AR expression was linked to invasive growth (p<0.0001) and nodal metastasis in urothelial carcinoma (p=0.0052). Conclusion: The results of our study demonstrate AR expression in a wide range of cancers. AR expression occurs most frequent in cancers of the prostate, breast, and ovary, but can be found in many types of non-prostate and non-gynecological neoplasms. The poor prognosis of breast and kidney cancers with reduced AR expression argues against a tumor promoting role of AR in these tumor types. Citation Format: Florian Viehweger, David Dum, Anne Menz, Ria Uhlig, Andrea Hinsch, Doris Höflmayer, Tim Mandelkow, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Sören Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till S. Clauditz, Till Krech, Andreas H. Marx, Ronald Simon, Stefan Steurer, Eike Burandt, Sarah Minner. Androgen receptor (AR) is frequently found in human cancers and inversely linked to patient outcome in breast and renal cell carcinomas. [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 5563.