Correlation between ERG Fusion Protein and Androgen Receptor Expression in Prostate Cancer; Possible Role in Diagnosis and Therapy
Amir Hassan Navaei, Phyu P Aung, Beatriz A Walter, Peter Pinto, Maria J Merino. NCI/NIH, Bethesda
Background: Prostate cancer (PC) is the second cause of cancer and cancer deaths in males in US. Recent discovery of fusion genes brought a new look to the pathogenesis of PC. Gene fusions occur nearly in 60% of PC with the TMPRSS2:ERG being the most common. Evidence supports the role of ERG fusion in tumorigenesis, progression and invasion of PC via effecting pathways such as C-MYC, PI3K/PTEN/AKT axis, uPA, TLR4 and Androgen receptor (AR) mediated signaling. Fusion related ERG over expression is dependent on existence of AR. In this study we evaluate by IHC, AR and ERG fusion on prostate core biopsies and prostatectomies with a wide range of pathological grades to investigate clinicopathological applications as well as their possible role in therapy.
Design: Ninety two biopsies and corresponding prostatectomies from 38 patients were studied as well as 2 lymph node metastasis. IHC was performed utilizing two highly specific ERG mAbs (EPR 3864;Epitomics,CA) and 9FY (Biocare LLC,CA). Fifty six matching biopsies and the corresponding prostatectomies were stained with AR mAb (AR441,Dako,CA). Percentage and intensity of staining rated from 0 to 3. Correlation with FISH for ERG fusion was done.
Results: Twelve of the 92 biopsies were benign, 15 had atypical glands and PIN, 43 were adenocarcinomas (AC) Gleason 6-7 and 32 were Gleason 8-10. Twenty two of 75 AC stained for ERG(29%); 17 were Gleason 6-7(77%) and 5 Gleason 8-10(23%). None of benign biopsies stained with ERG. Forty four of 59 matching biopsies with AC; 20/27(45%) Gleason 6-7, 17/17(38%) Gleason 8-10 and 9/11 atypical glands stained with AR (p<0.05). Among matching biopsies 8/25(32%) Gleason 6-7, 3/17(17%) Gleason 8-10 and 1/9(11%) atypical glands stained with both ERG/AR. All ERG positive biopsies were also positive with AR however 1 prostatectomy and 2 biopsies were ERG positive but AR negative. The two lymph node metastasis were positive for ERG/AR expression, consistent with the prostatectomy.
Conclusions: We conclude from our study that ERG assessment by IHC is useful for characterization of ERG status in prostate biopsies, and that the presence of fusion protein correlates with AR expression. These markers may assist in diagnosis since none of the benign biopsies stained with ERG. AR negative, ERG positive cases are rare. There is excellent correlation for ERG/AR staining between biopsies and prostatectomy specimen which suggests that the staining may have important clinical utility and assist in the development of new therapeutic targets.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 165, Monday Morning