TMPRSS2:ERG Rearrangement and Markers of Metabolic Signaling Pathways Implicated in Prostate Carcinogenesis.
Andreas Pettersson, Richard Flavin, Jennifer Stark, Michelangelo Fiorentino, Michael Pollak, Kathryn Penney, Howard D Sesso, Martin Gleave, Tarek A Bismar, Sven Perner, Stephen Finn, Mark A Rubin, Jing Ma, Edward Giovannucci, Meir Stampfer, Philip Kantoff, Massimo Loda, Lorelei Mucci. Dana Farber/Harvard Cancer Center, Boston, MA
Background: The common gene fusion TMPRSS2:ERG may act in concert with other key molecular events in the initiation and progression of prostate cancer. We examined if perturbation of metabolic signaling pathways, including expression of the Insulin receptor (IR), IGF-1 receptor (IGF1R), Adiponectin receptor 2 (AdipoR2), and fatty acid synthase (FASN), is associated with TMPRSS2:ERG rearrangements.
Design: We studied 392 men with prostate cancer. TMPRSS2:ERG status, by chromosomal translocation or intronic deletion, was assessed by an ERG break-apart FISH assay on tissue microarrays. Protein expression of IR, IGF1R, AdipoR2 (manual assessment), and FASN (semi-automated assessment) was evaluated by immunohistochemistry. We used the Wilcoxon rank-sum test to assess the differences in intensity of expression of these biomarkers among rearrangement positive versus negative tumors.
Results: In total, 40% of the tumors were rearrangement positive, with two-thirds occurring through deletion. Tumors harboring the ERG rearrangement had higher protein tumor expression of IR (P<0.001), IGF1R (P<0.001), AdipoR2 (P=0.03) (Figure 1), and FASN (P=0.009) (Figure 2). All these associations were more pronounced for rearrangement through deletion. There were no alterations in expression of these markers noted in the adjacent normal in rearrangement positive versus negative tumors.
Conclusions: TMPRSS2:ERG rearrangement is associated with upregulation of the IR, IGF1R, AdipoR2, and FASN. These observations suggest that TMPRSS2:ERG rearrangement, particularly through deletion, is associated with altered metabolic signaling pathways implicated in prostate carcinogenesis.
* Shared senior authorship
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 104, Monday Afternoon