ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification

Abstract

Gene fusions prevalent in prostate cancer (CaP) lead to the elevated expression of the ERG proto-oncogene. ERG activation present in 50–70% of prostate tumors underscores one of the most common oncogenic alterations in CaP. Despite numerous reports of gene fusions and mRNA expression, ERG oncoprotein status in CaP still remains to be defined. Furthermore, development of ERG protein-based assays may provide a new dimension to evaluation of gene fusions involving diverse androgen-regulated promoters and the ERG protein-coding sequence. Through exhaustive evaluations of 132 whole-mount prostates (261 tumor foci and over 200 000 benign glands) for the ERG oncoprotein nuclear expression, we demonstrated 99.9% specificity for detecting prostate tumor cells using a highly specific anti-ERG monoclonal antibody. The ERG oncoprotein expression correlated well with fusion transcript or gene fusion in randomly selected specimens. Strong concordance of ERG-positive foci of prostatic intraepithelial neoplasia (PIN) with ERG-positive carcinoma (82 out of 85 sections with PIN, 96.5%) affirms the biological role of ERG in clonal selection of prostate tumors in 65% (86 out of 132) of patients. Conversely, ERG negative PINs were associated with ERG-negative carcinoma. Taken together, the homogeneous and strong ERG expression detected in individual tumors establishes the potential for ERG oncoprotein-based stratification of CaP.

ERG protein expression and genomic rearrangement status in primary and metastatic prostate cancer—a comparative study of two monoclonal antibodies

“…The following clones and primary antibodies were used: anti-ERG rabbit monoclonal antibody (1:100 dilution, clone EPR3864, Abcam, Cambridge, MA, USA) 21 and anti-ERG mouse monoclonal antibody (1:1000 dilution, CPDR ERG-MAb, clone 9FY, CPDR, Rochville, MD, USA). 19 Dilution was Figure 1. A lymph node metastasis of an ERG-rearranged prostate cancer (PCa) (arrowheads) stained using the mouse monoclonal anti-ERG antibody (ERG-MAb) (a) and the rabbit ERG-MAb (b), respectively.…”

“…So far, two monoclonal ERGspecific antibodies (that is, mouse monoclonal anti-ERG antibody (ERG-MAb) and rabbit ERG-MAb) have been established on prostatic tissues. Furusato et al 19 reported a highly specific mouse ERG-MAb performing a comprehensive evaluation of ERG protein expression using whole mount prostate sections from 132 PCa cases. The ERG protein expression pattern showed a strong concordance with ERG fusion transcripts by branched DNA assay or ERG rearrangement by fluorescence in-situ hybridization (FISH) in selected specimens.…”

PTEN losses exhibit heterogeneity in multifocal prostatic adenocarcinoma and are associated with higher Gleason grade

“…[13][14][15] The TMPRSS2-ERG gene fusion is the principle genomic alteration and a characteristic signature in approximately half of all prostate cancers. 14,[16][17][18][19][20][21][22][23] ERG regulates matrix metalloproteinases, thus influencing extracellular matrix remodeling and the invasive potential of malignant cells. [24][25][26][27] PTEN is among the most commonly mutated tumor suppressor genes in human cancer.…”

Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma

“…[18][19][20] Several studies have shown anti-ERG antibody useful for prostate carcinoma, metastatic and primary, and prostatic intraepithelial neoplasias. [10][11][12]21,22 The detection of ERG is highly correlated with both ERG rearrangement by fluorescence in-situ hybridization and with ERG mRNA overexpression. 10,12,21 Similar to FLI1, ERG is also found to be expressed in both benign and malignant vascular tumors serving as a helpful marker for endothelial differentiation.…”