Abstract 2227: Concordance of ERG gene rearrangements and ERG protein expression in low grade PIN lesions in prostate needle biopsies
Authors: Nagy Dea , Nagle Ray , Garsha Karl , Christopherson Kelly , Riley Janice , Sathyanarayana Ubaradka , Cortez Connie , Smith Kassie , Pozarowski Krystyn , Yun Steven , Dittamore Ryan , Palanisamy Nallasivam , Sokoloff Mitchell , Demichelis Francesca , Rubin Mark , Miller Phil , Pestano Gary 
Published: June 2012

Abstract
TMPRSS2:ERG gene rearrangements are an early even found in 50% of prostate cancer patients. Identifcation of men who are at elevated risk of progression from neoplastic PIN (prostatic intraepithelial neoplasia) lesions to prostate carcinoma is an unaddressed, unmet medical need which may directly impact the practice of needle biopsy sampling and PSA screening. Previous studies have identified the presences of ERG rearrangements in ∼15% of High Grade PIN. In addition, ERG rearranged PIN lesions are highly associated with gene rearrangements in adjacent tumor foci on prostatectomy specimens. ERG gene rearrangements and protein over-expression in PIN may be associated with cancer in-situ, or may identify men who are at risk of more rapidly developing prostate carcinoma.
The goal of this study was to identify the extent of ERG rearrangements in PIN lesions of the prostate. We selected to develop automated staining procedures to detect ERG over-expression by immunohistochemistry (IHC), as well as the specific gene rearrangements by a FISH assay. To this end, probes specific to the ERG gene rearrangements including 3’ and 5’ ERG, were detected with quantum dot (LifeTechnologies) bioconjugates. Fixatives commonly used in preservation of needle biopsies as well as fixation times were also evaluated. Specific FISH signals were deconvolved using an interferometer and spectral imaging software.
We have shown sensitive and specific detection of gene rearrangements with this testing method in the xenograft models, VCaP, H660, and LNCaP, as well as in samples from prostate needle biopsies, and radical prostatectomies. In 6 of 88 prostate specimens, the ERG IHC was diagnostic of Low Grade PIN that was missed on initial examination of the H&E stain. Over-expression of ERG was not significantly associated with any specific type of gene rearrangement, including insertions or deletions in the 5’ region of the ERG gene. The ERG FISH test assessed rearrangements include: no rearrangement (normal), translocation through insertion, and translocation through deletion.
In summary, the new anti-ERG immunohistochemistry assay coupled with the ERG FISH provide a highly sensitive and specific reflex test format that may have utility subsequent to the initial H&E, in detecting clinically relevant diagnostic markers in PIN lesions. Identification of gene rearrangements and ERG protein over-expression in Low Grade PIN may help define a new class of prostate disease. This test format may help identify men who should be considered for more aggressive monitoring, for example through re-biopsying and active PSA screening. Studies are in progress to evaluate this testing strategy for prognostic value in assessing prostate cancer progression associated with the incidence of PIN in selected prostate cancer and biopsy cohorts. At time of submission, assay is not approved for use in the US.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2227. doi:10.1158/1538-7445.AM2011-2227