ERG-TMPRSS2 Rearrangement Is Shared by Concurrent Prostatic Adenocarcinoma and Prostatic Small Cell Carcinoma and Absent in Small Cell Carcinoma of the Urinary Bladder.
Sean R Williamson, Shaobo Zhang, Jorge L Yao, Jiaoti Huang, Antonio Lopez-Beltran, Steven Shen, Adeboye O Osunkoya, Gregory T MacLennan, Rodolfo Montironi, Liang Cheng. Indiana University, Indianapolis; University of Rochester; University of California at Los Angeles; Cordoba University, Spain; The Methodist Hospital, Houston; Emory University, Atlanta; Case Western Reserve University, Cleveland; Polytechnic University of the Marche Region, Ancona, Italy
Background: Prostatic carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic small cell carcinoma (SmCC) is a rare variant with aggressive behavior. Distinction between SmCC of the prostate and urinary bladder may be challenging, especially in small biopsy specimens without associated prostatic adenocarcinoma or urothelial carcinoma. Recently, gene fusions between ETS genes, particularly ERG, and TMPRSS2 have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of SmCC.
Design: Twenty-nine cases of prostatic SmCC from the authors' archives were studied, among which 13 had coexisting prostatic adenocarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3'/5' ERG and TMPRSS2. 25 cases of bladder SmCC were also tested.
Results: ERG gene alterations were found only in prostate malignancy and not in benign prostate tissue or bladder SmCC. TMPRSS2-ERG gene fusion was found in 48% (14/29) of prostatic SmCC. Of cases with concurrent prostatic adenocarcinoma, 85% (11/13) had identical findings in both components. In 10% of cases, rearrangement was associated with 5' ERG deletion. In 17% (5/29), gain of chromosome 21q was present. Two cases (7%) showed discordant aberrations in the SmCC and adenocarcinoma, 1 with deletion of 5' ERG and 1 with gain of chromosome 21q, both in only the adenocarcinoma component.
Conclusions: SmCC of the prostate demonstrates TMPRSS2-ERG rearrangement with comparable frequency to prostatic adenocarcinoma. In cases with concurrent adenocarcinoma and SmCC, 85% showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in 2 cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for phenotypic variation. TMPRSS2-ERG fusion is absent in bladder SmCC, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic SmCC of unknown origin.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 151, Monday Afternoon