CXCR4 mRNA overexpression in high grade prostate tumors: Lack of association with TMPRSS2-ERG rearrangement

Article type: Research Article

Authors: de Muga, Silvia^{a; e;} | Hernández, Silvia^{b; ; *} | Salido, Marta^c | Lorenzo, Marta^a | Agell, Laia^a | Juanpere, Núria^a | Lorente, José A.^{d; f} | Serrano, Sergio^{a; f} | Lloreta, Josep^{a; b}

Affiliations: [a] Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain | [b] Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain | [c] Molecular Cytogenetics Laboratory, Department of Pathology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain | [d] Department of Urology, Hospital del Mar-Parc de Salut Mar-IMIM, Barcelona, Spain | [e] Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Barcelona, Spain | [f] Department of Morphologic Sciences, Autonomous University of Barcelona, Barcelona, Spain

Correspondence: [*] Corresponding author: Silvia Hernández, Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Passeig Maritim 25-29, 08003-Barcelona, Spain. Tel.: +34 93 248 30 31; Fax: +34 93 248 31 31; E-mail: [email protected].

Note: [1] The two first authors have contributed equally to this paper.

Abstract: The TMPRSS2-ERG fusion has been reported in 42 to 78% of prostate tumors. More than 90% of ERG-overexpressing tumors harbor the fusion. The relationship between the TMPRSS2-ERG fusion and prognosis is controversial. Different studies have suggested an association between CXCR4 and ERG overexpression resulting from the TMPRSS2-ERG rearrangement. The aim of this study was to investigate the relationship between CXCR4 expression, TMPRSS2-ERG fusion and Gleason grade in prostate cancer. TMPRSS2-ERG rearrangement was investigated by FISH (n=44), ERG protein by IHC (n=84), and CXCR4 by quantitative RT-PCR (n=44). TMPRSS2-ERG rearrangement and ERG protein expression were present in almost 50% of the cases, without statistical differences between the different Gleason score groups. There was a very high concordance between FISH and IHC techniques (Kappa Index=0.954). Seventy percent of Gleason ⩾ 8 prostate tumors overexpressed CXCR4 mRNA, and the difference in CXCR4 expression with Gleason < 8 cases was statistically significant (p=0.009). There was no association between ERG protein and CXCR4 mRNA expression. In conclusion, our results reveal for the first time that CXCR4 overexpression is associated with high Gleason score prostate tumors, but that it is independent of the TMPRSS2-ERG rearrangement.

Keywords: CXCR4, TMPRSS2, ERG, rearrangement, overexpression, prostate cancer

DOI: 10.3233/CBM-2012-00288

Journal: Cancer Biomarkers, vol. 12, no. 1, pp. 21-30, 2013