Quantitative expression of TMPRSS2 transcript in prostate tumor cells reflects TMPRSS2–ERG fusion status

Abstract

TMPRSS2-ERG fusion is the most common oncogenic rearrangement in prostate cancer (CaP). Due to this chromosomal rearrangement one TMPRSS2 allele loses its promoter, and one of the ERG alleles gains that promoter leading to its overexpression in these tumor cells. Some studies suggest that TMPRSS2, an androgen regulated type II trans-membrane serine protease, may have an effect on CaP progression. We hypothesized that a difference in TMPRSS2 expression may be present in vivo between CaP cells with and without TMPRSS2-ERG fusion, or a compensatory mechanism for the allelic loss of TMPRSS2 may balance that expression difference. Therefore, TMPRSS2 mRNA expression was evaluated in micro-dissected CaP cells with and without TMPRSS2-ERG fusion in 132 CaP patients and analyzed for its correlation with other androgen receptor (AR) regulated genes and clinico-pathologic features. In vivo TMPRSS2 expression correlated with that of other AR-regulated genes, including PSA/KLK3 and PMEPA1, offering potential as AR surrogates. A significantly reduced expression of TMPRSS2 was evident in malignant cells harboring TMPRSS2-ERG fusion, but not in CaP cells without TMPRSS2-ERG fusion, further defining these two genetically distinct types of CaP.