Abstract
Abstract The multifocality and highly variable molecular pathology of prostate cancer are underlying features of this clinically heterogeneous disease. Most patients harbor multiple molecularly distinct cancer foci at diagnosis that likely arose as independent clones. There is a critical need for molecular biomarkers that can distinguish the multifocality and inter-focal heterogeneity of tumors and help stratify patients for treatment. PTEN loss and ETS gene rearrangements are among the most prevalent genomic alterations in prostate carcinogenesis. The detection of both ERG overexpression and PTEN protein loss by immunohistochemistry (IHC) have proven to be reliable substitutes for detecting genomic alterations by fluorescence in situ hybridization (FISH) assay. We developed monoclonal antibodies against ETV1 and ETV4 and evaluated their performance in prostate cancer specimens. The expression of ETV1, ETV4, were examined in relation to ERG and loss of PTEN expression in TMAs constructed from primary prostate cancer specimens of two independent patient cohorts. The first TMA was constructed from multiple 1 mm cores representing distinct tumor focus from multifocal tumors from 50 African American (AA) and 50 Caucasian American (CA) men. The second was constructed from a single 2 mm core of individual tumors from an independent cohort of 152 AA and 304 CA men. We present results on the expression of each protein biomarker in the context of patient race and their association with clinico-pathologic features, together with concurrence or mutual exclusiveness for each event. These results support the application of ETS monoclonal antibodies in IHC assays to detect prostate cancer tumor heterogeneity and to identify subsets of prostate cancer. Citation Format: Cara Schafer, Denise Young, Yingjie Song, Jiji Jiang, Albert Dobi, Gyorgy Petrovics, Bettina F. Drake, Gregory T. Chesnut, Isabell A. Sesterhenn, Shyh-Han Tan. Immunohistochemical detection of prostate cancer heterogeneity by using ETS and PTEN monoclonal antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2220.
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