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Correlation between ERG Fusion Protein and Androgen Receptor Expression by Immunohistochemistry in Prostate, Possible Role in Diagnosis and Therapy

2017-08-13 17:56:07

Wiley Online Library; 13 August 2017 DOI: 10.7150/jca.16751

TAmir Hassan Navaei1, Beatriz A Walter1, Vanessa Moreno1, Svetlana D Pack1, Peter Pinto2, Maria J
Merino



Abstract


Background: Recent discovery of gene rearrangements have brought a new look to the
molecular pathogenesis of cancer. Gene fusions occur in nearly 60% of prostate adenocarcinoma,
being the TMPRSS2-ERG one of the most common. Evidence supports the role of ERG fusion in
tumorigenesis, progression and invasion via effecting pathways such as WNT, MYC, uPA,
PI3K/AKT/PTEN, RAS/RAF/MAPF, NKX3.1, GST-pi and androgen receptor (AR) mediated signaling.
Most of the ERG fusions involve 5’-partners androgen responsive. Therefore, we aimed to evaluate
AR and ERG fusion protein expression on prostate tissue to find clinicopathological applications
and possible role in therapy.


Methods: One hundred three samples, including prostate core biopsies and radical
prostatectomy specimens, were evaluated for ERG and AR expression by immunohistochemistry
(IHC). ERG rearrangement was done by fluorescence in situ hybridization (FISH) on 11 randomly
selected cases and correlated with IHC results.


Results: From the total of 103 samples, eight (8/103) were benign, fourteen (14/103) had atypical
glands, two (2/103) had prostatic intraepithelial neoplasia (PIN), and seventy nine (79/103) showed
prostate adenocarcinoma. Forty four (44/79) tumor cases were Gleason score (GS) 6-7 (lower
GS), and thirty five (35/79) were GS of 8-10 (higher GS). ERG immunoreaction was observed in
27.8% (22/79) of the tumor cases, showing higher expression in those with lower GS (68.2%,
15/22) compared to higher GS (31.8%, 7/22). Neither benign glands nor PIN stained with ERG. AR
expression was observed in 75% of benign samples, 78.5% of atypical glands, 100% of PIN, and in
87.3% of tumor cases with no significant difference based on GS. Co-expression of ERG and AR
was evaluated on all the tumor samples. ERG+/AR+ was seen in 77.3% (17/22) of the ERG+ tumor
cases, with higher frequency in lower GS (64.7%, 11/17) compared to those with higher GS (35.3%,
6/17). All but five corresponding ERG+ tumor samples were negative for AR. Only 5 samples were
ERG-/AR- corresponding to adenocarcinoma GS of 6. Presence or absence of ERG rearrangement
was confirmed by FISH and correlated with IHC results.


Conclusions: Characterization of ERG status by IHC in prostate tissue has an excellent
correlation with FISH. It may also assist in diagnosis since none of the benign glands stained with
ERG. Co-expression of ERG+/AR+ in prostate tumor by IHC may suggest gene fusion between ERG
and a 5’-partner driven by androgen signaling such as TMPRSS2, which it could represent an
important ancillary test for clinical management and development of new therapeutic targets.



Empire Genomic's ERG Break Apart FISH Probe was used in this publication.

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