ERG Oncoprotein Overexpression in Matched Primary and Metastatic Prostate Adenocarcinomas.
Bora Gurel, Helen Fedor, Jessica L Hicks, Angelo M De Marzo. Johns Hopkins University School of Medicine, Baltimore
Background: Gene fusions of Ets family members to the androgen-regulated TMPRSS2 gene is a common occurrence in prostate cancer. The most common fusion is between TMPRSS2 and ERG, which occurs in roughly 50% of prostate cancers. Until recently, little was known regarding the expression of the ERG protein. Two recent reports indicate robust staining for ERG protein in a subset of prostate cancers and that this correlates highly with FISH-verified rearrangements (Prostate Cancer and Prostatic Diseases, 13:228–237,2010; Neoplasia, 12:590-598,2010). However, whether untreated metastatic prostate cancers are also ERG protein positive has only been examined in 7 cases thus far.
Design: For this study, we constructed a TMA using primary prostate adenocarcinoma tissues from 37 radical prostatectomy specimens and matched, hormone-naïve metastatic prostate carcinoma tissues from accompanying pelvic lymph node dissections, using the largest tumor nodule from each case. The TMA slide was stained with a rabbit monoclonal antibody (Epitomics), digitized and uploaded into TMAJ for web-based analysis. Each TMA spot was then visually assessed for ERG oncoprotein immunopositivity in the carcinoma lesion.
Results: As shown previously, there was strong staining in virtually all endothelial cells yet no staining was present in normal prostate epithelium. In most positive cases, virtually all of tumor cells showed robust nuclear staining. Of the 37 primary carcinomas, 27 (73%) were positive for ERG. Of these 27, 24 (88.9%) of the matched lymph node metastases were positive, whereas 3 were negative. Of the primary tumors that were negative for ERG, all corresponding lymph nodes were negative. There were no cases where only the lymph node metastasis was positive with the primary being negative.
Conclusions: Our results show that ERG protein positivity in a primary index tumor is mirrored to a large extent in corresponding untreated lymph node metastases. Since there were no cases of positively staining lymph node metastases without a corresponding primary tumor being positive, these results support prior studies indicating that ERG alterations resulting in ERG protein overexpression occur early during prostate carcinogenesis. Thus, unlike other molecular alterations in prostate cancer that occur more frequently in progressive disease (e.g. PTEN loss and 8q24 gain), a given prostatic adenocarcinoma lesion either does or does not have ERG protein overexpression, and if it does, it occurs very early in the process and is maintained across disease states.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 100, Monday Afternoon