XMRV Is Present In Malignant Prostatic Epithelium And Is Associated With Prostate Cancer, Especially High-Grade Tumors

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 30 Nov 2009 - 7:00 PST

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UroToday.com - In the September 22, 2009 issue of the Proceedings of the National Academy of Sciences, Dr. Robert Schlaberg and colleagues verify that the DNA and protein from the xenotropic murine leukemia virus-related virus (XMRV) exists in prostate cancer (CaP) tissue.

The initial report in 2006 linked the gammaretrovirus XMRV in CaP patients with reduced activity against the RNASEL gene. A strong correlation between the R462Q variant and XMRV was present; XMRV 89% of XMRV positive cases and only 16% of XMRV negative cases were homozygous (QQ) for this variant. While only CaP specimens were evaluated in the initial report, the present study also assessed benign prostate tissue.

The investigators developed a molecular clone of XMRV, called pXMRV1 and demonstrated that it could replicate in LNCaP cells. The particles released from XMRV-infected cells showed morphology consistent with type-C retroviral cores. To determine the presence of XMRV in clinical samples, 233 CaP and 101 benign prostate samples were studied. Quantitative PCR amplified XMRV proviral DNA from tissue. XMRV DNA was detected in 14 cases (6.2%) of CaP and in 2 cases (2.0%) of benign cases. Calculations determined that each 10-μm section from a CaP sample contained the same amount of proviral DNA as 6-7 XMRV-infected cultured cells. Immunohistochemistry using XMRV-specific antisera was performed on prostate samples from XMRV PCR positive cases and in cell cultures to validate the assay. In the CaP cases, 54 (23%) had XMRV protein expression compared with 4 (4%) of controls. XMRV protein was in the epithelial cells in 46 tumors (85%), in both epithelial and stromal cells in 4 tumors (7.5%), and only in stromal cells in another 4 tumors (4%). XMRV positivity was 5-fold higher in CaP than in benign controls, and was positive in 18% of Gleason score 6 tumors, 27% of Gleason score 7 tumors, 29% of Gleason score 8 tumors, and 29% of Gleason score 9 tumors. There were no significant differences between cases and controls regarding the RNASEL R462Q variant. This means the at risk population for XMRV infection increases from only men with the RNASEL variant to all men.

Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR

Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16351-6.
doi:10.1073/pnas.0906922106

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Contributing Editor Christopher P. Evans, MD, FACS

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