XMRV and Prostatic Adenocarcinoma: Is There Really a Link?
AO Osunkoya, RS Arnold, NA Johnson, NV Makarova, S Suppiah, TA Scott, S Bhosle, E Hunter, H Ly, RJ Molinaro, JL Blackwell, D Liotta, FF Marshall, JA Petros. Emory University School of Medicine, Atlanta, GA
Background: The recent discovery of Xenotropic Murine Retrovirus (XMRV) in patients with prostate cancer (PCa) is notable because it leads to the intriguing hypothesis that XMRV is a new cancer causing virus. There has been considerable difficulty in replicating the initial reports of this virus in PCa, leading some to question the validity of prior studies.
Design: We preformed PCR of XMRV-specific sequences on banked frozen prostate tissue derived from patients that had radical prostatectomy as monotherapy for PCa at our institution. 420 DNA samples from prostatectomy specimens were analyzed for the R462Q RNase L variant of RNASEL, the familial PCa gene thought to predispose to XMRV infection and thus PCa. In a subset of these patients, confirmatory FISH analysis was performed on adjacent sections to directly visualize the presence or absence as well as cellular localization of XMRV nucleotide sequences. Immunohistochemical stains (IHC) for XMRV protein was also performed. A fluorescent cell infection assay was developed to test selected patients' serum for the presence of antibodies capable of neutralizing XMRV infection. A tissue microarray constructed from 104 PCa patients unrelated to the initial group was also stained for the XMRV protein.
Results: 187 (45 %) patients were found to be homozygous wild type (RR), 185 (44 %) patients were heterozygous (RQ), and 48 (11%) patients were homozygous mutant (QQ) at the critical amino acid of the HPC1 gene RNASEL. We then selected a small cohort of QQ patients to analyze by multiple methods, ultimately resulting in 6 patients with definitive results in all 4 assays (PCR, FISH, serology and IHC). There was complete concordance of all 4 methods of detecting infection in all 6 patients with 4 being positive for XMRV viral infection and 2 being negative. PCa specimens found to be positive for XMRV DNA sequences by PCR and confirmed by FISH of adjacent sections, also had high titers of neutralizing antibodies in their serum and XMRV proteins in their malignant glandular epithelium by IHC. 5 of the 104 unrelated patients with PCa stained positive for XMRV protein.
Conclusions: XMRV viral infection though relatively uncommon, is confirmed to exist in clinical specimens of patients with PCa. The XMRV virus infects and replicates in prostatic tissue. A strong correlation exists between DNA, IHC, FISH positive patients and high titers of neutralizing antibodies detectable in serum.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 1:00 PM
Poster Session II # 104, Monday Afternoon