Clinical Applications of Novel ERG Immunohistochemistry in Prostate Cancer Diagnosis and Management

Abstract

TMPRSS2:ERG gene fusions, the most common molecular subtype of ETS family gene fusions occur in ~50% of prostate carcinomas (PCas) and ~20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. ERG gene fusions have not yet been demonstrated in isolated benign prostate tissue, isolated high-grade prostatic intraepithelial neoplasia, or benign cancer mimics. Taken together, ERG gene fusions are the most prostate cancer-specific biomarker yet identified and define a specific molecular subtype of PCa with important clinical and biological implications. ERG gene fusions result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG protein product. Recently, N-terminal epitope-targeted mouse (9FY) and C-terminal-targeted rabbit monoclonal (EPR 3864) ERG antibodies are commercially available and are increasingly utilized as a surrogate for TMPRSS2:ERG gene fusions. Until recently, because of lack of availability of reliable ERG antibody, the most commonly utilized methods for studying ERG aberrations in PCa specimens included fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. The knowledge gleaned from these studies has significantly improved our understanding of molecular biology of ERG gene fusions. With availability of highly specific anti-ERG monoclonal antibodies, there are now unprecedented opportunities to explore and validate clinical applications of ERG antibody in routine pathology practice, which has just started. This review provides a brief background of molecular biology of ERG gene fusions in PCa and focuses on characterizing the current state of ERG oncoprotein and determining the role of ERG immunohistochemistry in the diagnosis and biological stratification of prostate cancer.

Frequency of ERG-positive prostate carcinoma in Poland

“…Some authors have proposed diagnostic and prognostic use of ERG immunohistochemistry [5,[22][23][24][25].…”

Novel uses of immunohistochemistry in the diagnosis and classification of soft tissue tumors

“…12 ERG is also positive in a selected group of tumors that harbor translocations involving ERG: B50% of prostatic adenocarcinomas, 5-10% of Ewing sarcomas, and a small subset of acute myeloid leukemias. 13 Brachyury (T) is a transcriptional activator involved in the development of the notochord. 14 Nuclear expression of brachyury is a consistent feature of chordoma ( Figure 3), which is a helpful diagnostic immunohistochemical finding to distinguish this tumor type from potential histologic mimics, including chondrosarcoma, metastatic carcinoma, and myoepithelial tumors.…”

Molecular Clues Assist in the Cancer Clinic

“…In prostatectomy specimens, ERG expression is rarely, if ever, detected in benign glands. Evaluation of ERG staining in needle biopsy specimens conf rmed the cancer-specif city of ERG expression, and IHC for ERG is now being used for diagnostically challenging PCa cases (3,4).…”