Detection of TMPRSS2 Gene Deletions and Translocations in Carcinoma, Intraepithelial Neoplasia and Normal Epithelium of the Prostate by Direct Fluorescence In Situ Hybridization
S Zhang, B Pavlovitz, J Tull, Y Wang, C Fuller. SUNY Upstate Medical University, Syracuse, NY; College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China
Background: TMPRSS2 gene fusions with ETS-transcription factor family members ERG, ETV1 or ETV4 have been recently discovered as a common molecular event in prostate cancer. Much attention has been focused on exploring their clinical application as a genetic tumor marker for diagnosis, prognosis, and prediction of response to therapy. However, detection of TMPRSS2 genetic alterations using direct fluorescence in situ hybridization (FISH) has not been well studied. We examined cancers, intraepithelial neoplasia (PIN), and normal prostate epithelium to determine frequency, specificity, tissue heterogeneity, and prognostic value of the TMPRSS2 genetic alterations.
Design: 71 cases (161 samples) of normal prostate, 60 cases (153 samples) of PIN, and 61 cases (142 samples) of carcinoma in formalin-fixed paraffin-embedded tissue microarray were tested using a direct TMPRSS2 dual-color break-apart FISH probe cocktail. This FISH probe cocktail theoretically should detect all known TMPRSS2-associated deletions or translocations.
Results: 62% of prostate carcinomas demonstrated TMPRSS2 gene alterations, including 39% translocation, 16% deletion and 7% mixed patterns. Tissue heterogeneity for TMPRSS2 gene alterations was identified in 28% of prostate carcinomas. No difference in frequency of TMPRSS2 gene alterations was found between Gleason 6 and 7. 17% of PIN had TMPRSS2 gene alterations and presented the same FISH pattern as the corresponding carcinoma. None of 161 normal prostate samples showed TMPRSS2 translocation or deletion.
Conclusions: Direct TMPRSS2 dual-color break-apart FISH probe cocktail provides a simple and reliable method for detection of TMPRSS2-related genetic alterations in formalin-fixed paraffin-embedded tissue. TMPRSS2 genetic alterations detectable by this method are highly specific for prostate neoplasia, and can be identified in the majority of prostate carcinomas. Tissue heterogeneity for TMPRSS2 alterations is common, and it should be considered when sampling and evaluating biopsy specimens.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 1:00 PM
Poster Session II # 112, Monday Afternoon