ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer

Abstract

In prostate cancer genomic rearrangements involving genes encoding ETS transcription factors are commonly present, with androgen-regulated transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogen homologue (ERG) gene fusion occurring in 40-70%. Studies on the predictive value of ERG rearrangement as detected by in-situ hybridization or polymerase chain reaction have resulted in varying outcomes. The objective of this study was to correlate immunohistochemical ERG protein expression with clinico-pathological parameters at radical prostatectomy specimens, and to determine its predictive value for postoperative disease recurrence and progression in a prostate cancer screening cohort. Since androgen receptor is downregulated by ERG in cell lines, we also compared the expression of respective proteins. We selected 481 participants from the European Randomized Study of Screening for Prostate Cancer treated by radical prostatectomy for prostate adenocarcinoma. A tissue microarray was constructed containing representative cores of all prostate cancer specimens as well as 22 xenografts and seven cell lines. Immunohistochemical expression of ERG and androgen receptor was correlated with prostate-specific antigen (PSA), Gleason sum, pT-stage, surgical margins, biochemical recurrence, local recurrence, overall death and disease-specific death. ERG expression was detected in 284 patients (65%). Expression occurred significantly more frequent in patients with PSA r10 ng/ml (P ¼ 0.024). There was no significant association between ERG and Gleason sum, pT-stage or surgical margin status. PSA (P ¼ 0.011), Gleason sum (P ¼ 0.003), pT-stage (P ¼ 0.001) and surgical margin status (Po0.001) all had independent value for postoperative biochemical recurrence, while positive surgical margin (P ¼ 0.021) was the only independent predictor for local recurrence. ERG protein expression did not have prognostic value for the clinical end points in uni-and multivariate analyses. A positive correlation existed between ERG and androgen receptor expression in single tissue cores (Po0.001). In conclusion, immunohistochemical ERG expression has no predictive value for prostate cancer recurrence or progression after radical prostatectomy. Increasing ERG levels are associated with the upregulation of androgen receptor expression in clinical specimens.

Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer

“…11,32 ERG immunoreactivity was present in half of the primary prostate cancers being consistent with the frequency of TMPRSS2-ERG fusion and the findings of other immunohistochemical studies. 11,33,34 We found an expression of ERG in approximately half of the lymph node metastases similar to the study of Hoogland et al 33 with six out of nine lymph nodes expressing ERG. In distant metastases, fluorescence in situ hybridization analyses have shown an occurrence of TMPRSS2-ERG rearrangements in 25-35%.…”

Genomic Predictors of Outcome in Prostate Cancer

“…Ten studies reported the prognostic value of the gene fusion in radical prostatectomy (RP) cohorts [19][20][21][22][23][24][25][26][27][28]. In 6 of the 10 studies, TMPRSS2:ERG fusion status was not associated with outcome after surgery [19,21,22,24,27,29].…”

“…Ten studies reported the prognostic value of the gene fusion in radical prostatectomy (RP) cohorts [19][20][21][22][23][24][25][26][27][28]. In 6 of the 10 studies, TMPRSS2:ERG fusion status was not associated with outcome after surgery [19,21,22,24,27,29]. In one Urine-detected rearrangement associated with positive repeat biopsy aCGH = array comparative genomic hybridization; ADT = androgen-deprivation therapy; AS = active surveillance; BCR = biochemical recurrence; CRPC = castration-resistant prostate cancer; DSS = disease-specific survival; FISH = fluorescence in situ hybridization; HR = hazard ratio; IHC = immunohistochemistry; IMRT = intensity-modulated radiation therapy; NA = not applicable; NR = not reported; OS = overall survival; PCa = prostate cancer; PSA = prostate-specific antigen; RT-PCR = reverse transcriptase polymerase chain reaction; RP = radical prostatectomy; SNP = single nucleotide polymorphism; TURP = transurethral resection of prostate; WW = watchful waiting.…”

Altered DNA Methylation Landscapes of Polycomb-Repressed Loci Are Associated with Prostate Cancer Progression and ERG Oncogene Expression in Prostate Cancer

“…Recent work, however, failed to confirm that TMPRSS2:ERG correlates with adverse tumor characteristics and unfavorable prognosis (10,11). Nonetheless, this fusion is a likely initiating event in prostate cancer development representing a separate etiology with unique expression and epigenetic profiles (12)(13)(14).…”