Antibody EPR3864 is specific for ERG genomic fusions in prostate cancer: implications for pathological practice. Mod Pathol

Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
Modern Pathology (Impact Factor: 6.19). 04/2011; 24(8):1128-38. DOI: 10.1038/modpathol.2011.65
Source: PubMed


Genomic rearrangements involving genes encoding erythroblast transformation-specific transcription factors are commonly present in prostate cancer. The TMPRSS2-ERG gene fusion that leads to ERG overexpression occurs in ~70% of prostate cancers. Implementation of fusion gene detection in pathological practice, however, has been hampered by the lack of reliable ERG antibodies. The objective of this study was first to compare ERG immunohistochemistry using the recently described antibody EPR3864 with ERG mRNA by quantitative PCR and, second, to investigate ERG immunohistochemistry in diagnostic prostate cancer needle biopsies. We analyzed 41 primary prostate adenocarcinomas obtained by radical prostatectomy and 83 consecutive prostate cancer needle biopsies. In the prostatectomy specimens, immunohistochemical ERG expression was highly concordant with the ERG mRNA overexpression (sensitivity 100% and specificity 85%). ERG overexpression was due to TMPRSS2-ERG gene fusion in all cases. ERG protein expression was identified in 51/83 adenocarcinomas (61%) on needle biopsies. ERG expression was more frequent in tumors infiltrating ≥2 needle biopsies (P<0.001) or occupying ≥50% of a single biopsy (P=0.018). Expression of ERG also occurred in 11/21 (52%) high-grade prostate intraepithelial neoplasia lesions. In 5/87 (6%) needle biopsies containing benign secretory glands, weak ERG staining was focally observed. In all of these cases, respective glands were adjacent to adenocarcinomas. In conclusion, immunohistochemistry for ERG strongly correlated with ERG mRNA overexpression and was specific for prostate cancer on needle biopsies. Therefore, ERG immunohistochemistry is an important adjunctive tool for pathophysiological studies on ERG gene fusions, and might support the pathological diagnosis of adenocarcinoma in a subset of prostate needle biopsies.

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    • "Barros-Silva et al. used fluorescent in situ hybridization (FISH) to detect TMPRSS2-ERG rearrangement in a cohort of 200 biopsies and found an association with low PSA levels at diagnosis and low Gleason score [93]. In needle-biopsies immunohistochemical ERG detection can be used to discriminate prostate cancer from its mimickers, although the additional value to other markers such as p63, basal cell keratin 5, and AMACR is limited [92, 94–99]. In an active surveillance cohort of 265 men, Berg et al. found a strong correlation between ERG protein expression and disease-progression [100]. "
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    ABSTRACT: Prostate cancer is diverse in clinical presentation, histopathological tumor growth patterns, and survival. Therefore, individual assessment of a tumor's aggressive potential is crucial for clinical decision-making in men with prostate cancer. To date a large number of prognostic markers for prostate cancer have been described, most of them based on radical prostatectomy specimens. However, in order to affect clinical decision-making, validation of respective markers in pretreatment diagnostic needle-biopsies is essential. Here, we discuss established and promising histopathological and molecular parameters in diagnostic needle-biopsies.
    Full-text · Article · Aug 2014 · BioMed Research International
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    • "Reference N Assay Type [57] 50 FISH RP, TURP [63] 50 RT-PCR RP [30] 54 FISH TURP [64] 54 RT-PCR, FISH RP [10] 59 FISH RP [65] 59 RT-PCR RP [38] 65 FISH RP [66] 82 FISH, RT-PCR RP [67] 84 RT-PCR RP [53] 85 RT-PCR Mets [68] 88 FISH, RT-PCR RP [45] 90 IHC TURP [27] 94 FISH RP [16] 100 FISH Bx [46] 118 FISH RP [49] 122 FISH RP [69] 147 IHC RP [20] 150 FISH RP [51] 150 FISH RP [70] 158 RT-PCR Bx [7] 163 FISH RP [17] 165 RT-PCR RP [58] 178 FISH Bx [71] 180 IHC, FISH RP [59] 194 RT-PCR RP [54] 200 FISH Bx [60] 214 FISH RP, TURP [61] 226 RT-PCR RP [52] 248 FISH RP a 454 IHC RP [15] 481 IHC RP [8] 540 FISH RP [45] 1180 IHC RP Low AJCC stage (0 study) High AJCC stage (10 studies, 5540 men) [30] 54 FISH TURP [45] 90 IHC TURP [46] 118 FISH RP [31] 143 IHC, FISH RP [42] 184 TLDA RP [11] 209 IHC RP, Bx [4] 312 IHC TURP [39] 445 FISH RP [45] 1180 IHC RP [47] 2805 IHC RP No association with stage (35 studies, 6474 men) [40] 19 IHC RP [18] 26 RT-PCR RP [22] 41 IHC, PCR RP [38] 42 FISH RP [44] 45 RT-PCR RP [56] 45 RT-PCR RP [57] 50 FISH RP, TURP [64] 54 RT-PCR, FISH RP [10] 59 FISH RP [65] 59 RT-PCR RP [38] 65 FISH RP performed by Pettersson et al [45] across 19 studies and 5074 prostate cancers. Once again, conflicting evidence has been reported, with 8 studies (1078 men) [17] [18] [26] [39] [40] [45] [48] [49] showing a positive association and 1 study (150 men) [20] showing a negative association between ERG fusion and an adverse clinical outcome. "
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    ABSTRACT: TMPRSS2/ERG fusion is among the most frequent genetic anomalies in prostate adenocarcinomas. Although positive immunostaining for ERG has been shown to tightly correlate with ERG fusion status, the clinical and prognostic significance of a positive ERG stain remains undetermined. The significance of ERG immunostaining in 454 consecutive prostate adenocarcinomas from radical prostatectomies (RPs) using tissue microarrays, herein, is evaluated. A separate set of 59 cases of incidental prostate adenocarcinoma detected on transurethral resection of prostate with a Gleason score of 6 was also included. ERG translocation was significantly more common in peripheral zone cancer in comparison with cancer of the transitional zone (33% in RP versus 5% in transurethral resection of prostate specimens). In the RP cohort, although ERG positivity was significantly associated with younger age at presentation and lower prostate-specific antigen values, it showed no association with Gleason score or with pathologic stage. In multivariate analysis, biochemical recurrence was only associated with the final RP Gleason score and elevated prostate-specific antigen levels and was unrelated to neither ERG positivity or to its staining intensity. In our hands, ERG positivity was unrelated to either aggressive local tumor characteristics or a worse outcome. Our results, as well as an extensive review of the related literature showing conflicting findings, seem to indicate that ERG immunopositivity cannot be considered as an important prognostic factor in prostate cancer.
    Full-text · Article · Oct 2013 · Human pathology
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    • "ERG protein expression has been recently suggested to be reflective of ERG gene rearrangements in prostate cancer (PCA) documenting remarkable concordance between the two [1] [2] [3] [4] [5] [6]. The rearrangements between the androgen receptor-regulated gene TMPRSS2 (21q22.3) "
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    ABSTRACT: Background. The prognostic significance of ERG expression in prostate cancer (PCA) has generated mixed results. We sought to investigate the prognostic significance of ERG expression in a localized cohort of men with PCA. Material and Methods. We investigated ERG protein expression in a cohort of 198 men with localized PCA. ERG expression was correlated with patients' clinical outcome and several pathological parameters, including Gleason score (GS), pathological stage, surgical margin, and extra-capsular extension. Results. ERG expression was detected in 86/198 (43.4%) patients exclusively in neoplastic epithelium. Overall, ERG mean expression intensity was 1.01 ± 1.27 versus 0.37 ± 0.83 in acinar PCA compared to foamy type PCA (P < 0.001). In HGPIN, ERG intensity levels were comparable to those in foamy type PCA (0.13 ± 0.56) but significantly lower than those in acinar PCA (P < 0.001). ERG expression was significantly associated with extra-prostatic extension and higher pathological stage and showed a trend toward seminal vesicle invasion. Herein, ERG expression was documented in 50/131 (38.1%) patients with pT2 versus 30/55 (54.5%) patients with pT3 (P = 0.04). ERG association with higher pathological stage was more pronounced in patients with GS > 7. Grouping patients into those with GS ≤ 7 versus >7, there was no significant association between ERG expression and GS. Similarly, no association was present in relation to either surgical margins or postsurgical serum PSA levels. Conclusion. We report significant association between ERG protein levels and extra-prostatic extension and higher pathological stage. ERG expression is not associated with adverse clinical outcome and is of limited prognostic value in localized PCA.
    Full-text · Article · Aug 2013
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