Abstract 5258: Expression analysis of STEAP1 in breast cancer patients as therapeutic target

Abstract

Abstract Objective: The six transmembrane epithelial antigen of the prostate (STEAP1) is predominantly overexpressed in human prostate cancer. STEAP1 was first identified as a prostate-specific cell-surface antigen and found to be up-regulated in multiple cancer cell lines and in various cancers, including lung, bladder, colon and ovarian cancers. However no significant expression in normal tissue has been reported suggesting its potential use as a target for anti-STEAP1 immunotherapy. An anti-STEAP1 monoclonal antibody linked to an antimitotic agent is in Phase I clinical trials for prostate cancer patients. Microarray data from our lab suggested that STEAP1 is also highly expressed in human breast cancers. In this study we evaluate expression STEAP1 in primary tumors and the bone marrow from breast cancer patients as a therapeutic target for minimal residual disease. Experimental procedures: RNA was isolated from primary tumor and non-malignant breast tissue. RNA was also isolated from bone marrow of state II and III breast cancer patients, healthy volunteers and breast cancer cell lines. STEAP1 expression was analyzed by nanostring nCounter and real time qRT-PCR using human specific probes. STEAP1 immunohistochemical (IHC) staining of human tissue was performed using standard IHC Protocol. Results: STEAP1 mRNA was up-regulated in 77% of tumors (28/36) compared to the corresponding normal tissue. STEAP1 protein was expressed in 100% of tumors (8/8) and was absent in non-malignant breast tissue (7/7) by IHC staining. STEAP1 mRNA was not expressed normal BM, but was detected in 8% (6/74) of BM from patients with early stage breast cancer. Of patients with STEAP1 positive BM, 50% (3/6) had triple negative disease and 66% (4/6) developed recurrent disease (p = .028). Conclusion: STEAP1 is expressed in human breast tumors and the BM of breast cancer patients. Expression of STEAP1 in the BM is significantly associated with the development of metastatic disease. Our data indicate that STEAP1 could serve as a therapeutic target for the treatment of minimal residual disease in breast cancer. Citation Format: Chidananda Mudalagiriyappa, Sreeraj Pillai, Mark Watson, Rebecca Aft. Expression analysis of STEAP1 in breast cancer patients as therapeutic target. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5258. doi:10.1158/1538-7445.AM2015-5258