Arnold, R. S. et al. XMRV infection in prostate cancer patients: novel serologic assay and correlation with PCR and FISH. Urology 75, 755-761

Department of Chemistry, Emory University, Atlanta, Georgia, United States
Urology (Impact Factor: 2.13). 04/2010; 75(4):755-61. DOI: 10.1016/j.urology.2010.01.038
Source: PubMed

ABSTRACT To develop a serum-based assay to detect neutralizing antibodies to the xenotropic murine leukemia virus-related virus (XMRV) retrovirus and to use this assay with polymerase chain reaction and fluorescence in situ hybridization to identify patients with prostate cancer previously exposed to XMRV infection and those who carry XMRV viral sequences in their prostate.
Patients who had undergone radical prostatectomy were enrolled, and biologic specimens were obtained at surgery. The patients were genotyped for the R462Q RNASEL variant using a TaqMan genotyping assay on DNA from the peripheral blood. A serum assay that detects XMRV neutralizing antibodies was developed and used to determine which patients had serologic evidence of previous infection with XMRV virus. Some of these patients were also tested for the presence of XMRV nucleotide sequences in their prostate using polymerase chain reaction and fluorescence in situ hybridization analysis.
At a serum dilution of 1:150, our assay detected 11 (27.5%) of 40 patients with XMRV neutralizing antibodies, including 8 (40%) of 20 with the RNASEL genotype QQ and 3 (15%) of 20 with either the RQ or RR genotype. These results were in complete concordance with 2 other assays (polymerase chain reaction and fluorescence in situ hybridization), which were designed to detect XMRV infection.
XMRV infects some patients with prostate cancer. Neutralizing antibodies against XMRV correlated with 2 independent methods of detecting the virus in the prostate. The antibody response suggests that with clinical serologic assay development, it might be possible to screen patients for XMRV infection. The cases presented in the present report provided biologic samples that can be used for the development of a clinically relevant assay.

  • Source
    • "PCR assays described herein detected MLV provirus env sequences present in mouse genomic DNA (YAC-1 cells) agrees with result of other studies (Danielson et al., 2010; Tang et al., 2012; Rezaei et al., 2013). A high prevalence of XMRV has been reported in patients with prostate cancer and chronic fatigue syndrome (CFS) in the USA (Urisman et al., 2006; Schlaberg et al., 2009; Arnold et al., 2010). But, in Europe (Fischer et al., 2008; Hohn et al., 2009; Verhaegh et al., 2011), the USA, and recent study in Australia detection of XMRV in prostate (Aloia et al., 2010; Switzer et al., 2010; Rezaei et al., 2013), and breast cancer tissues (Khan et al., 2012) have been failed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Multiple etiologies have been hypothesized for prostate cancer, including genetic defects and infectious agents. A recently reported gamaretrovirus, xenotropic murine leukemia virus-related virus (XMRV) has been reported to be detected in prostate cancer. However, this virus has not been detected in similar groups of patients in other studies. Herein, we sought to detect XMRV in prostate cancers and benign controls in Sanandaj, west of Iran. Materials and Methods: In a case-control study, genomic DNA was extracted from formalin fixed and paraffin embedded prostate tissues from a total of 163 Iranian patients. We developed a conventional and a nested PCR assay using primers targeting to an env specific sequence of XMRV. PCR assays were carried out on 63 prostate cancers and 100 benign prostate hyperplasias. Results: Beta-actin sequences were successfully detected in the DNA extracts from all prostate tissues, confirming DNA extraction integrity. We did not detect XMRV in samples either from prostate cancers or benign prostate hyperplasias using XMRV specific primers. Conclusions: We conclude that in our population XMRV does not play a role in genesis of prostate cancer.
    Asian Pacific journal of cancer prevention: APJCP 11/2013; 14(11):6929-33. DOI:10.7314/APJCP.2013.14.11.6929 · 2.51 Impact Factor
  • Source
    • "The first of these is a gammaretrovirus, termed xenotropic murine leukaemia virusrelated virus (XMRV) discovered in human prostate carcinomas from patients who were homozygous for the anti-viral enzyme, ribonuclease L (Urisman et al, 2006). If confirmed, XMRV will become the fourth member of the retroviridae family to infect humans and the second to be associated with a human malignancy (Schlaberg et al, 2009; Knouf et al, 2009; Arnold et al, 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aetiology of breast cancer remains elusive. A viral aetiology has been proposed, but to date no virus has been conclusively demonstrated to be involved. Recently, two new viruses, namely Merkel cell polyomavirus (MCV) and xenotropic murine leukaemia virus-related virus (XMRV) have been identified and implicated in the pathogenesis of Merkel cell carcinoma (MCC) and familial form of prostate cancer, respectively. We examined 204 samples from 58 different cases of breast cancer for presence of MCV or XMRV by PCR. Samples consisted of both malignant and non-malignant tissues. Additionally, we included 6 cases of MCC and 12 cases of prostate cancer as potential controls for MCV and XMRV, respectively. All of the breast cancer samples examined were negative for both MCV and XMRV. However, 4/6 MCC and 2/12 prostate cancer samples were found to be positive for MCV and XMRV, respectively. Sequence analysis of the amplified products confirmed that these sequences belonged to MCV and XMRV. We conclude that there is no evidence for the involvement of MCV or XMRV in the pathogenesis of breast cancer. What role these viruses have in the pathogenesis of MCC and prostate carcinomas remains to be demonstrated.
    British Journal of Cancer 02/2012; 106(6):1166-70. DOI:10.1038/bjc.2012.51 · 4.82 Impact Factor
  • Source
    • "Findings from previous studies reporting higher prevalence for XMRV in similar cohorts [2] [11] [12] typically involved testing of prostate tumors. None of these studies reported the detection of XMRV in blood samples or the isolation of infectious virus from clinical specimens, and only one measured the presence of reactive antibodies through a virus neutralization assay [10]. Detection of antibody responses to specific viral proteins by ELISA or by reactivity to XMRV immunoblots was not assessed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The MLV-related retrovirus, XMRV, was recently identified and reported to be associated with both prostate cancer and chronic fatigue syndrome. At the National Cancer Institute-Frederick, MD (NCI-Frederick), we developed highly sensitive methods to detect XMRV nucleic acids, antibodies, and replication competent virus. Analysis of XMRV-spiked samples and/or specimens from two pigtail macaques experimentally inoculated with 22Rv1 cell-derived XMRV confirmed the ability of the assays used to detect XMRV RNA and DNA, and culture isolatable virus when present, along with XMRV reactive antibody responses. Using these assays, we did not detect evidence of XMRV in blood samples (N = 134) or prostate specimens (N = 19) from two independent cohorts of patients with prostate cancer. Previous studies detected XMRV in prostate tissues. In the present study, we primarily investigated the levels of XMRV in blood plasma samples collected from patients with prostate cancer. These results demonstrate that while XMRV-related assays developed at the NCI-Frederick can readily measure XMRV nucleic acids, antibodies, and replication competent virus, no evidence of XMRV was found in the blood of patients with prostate cancer.
    Advances in Virology 11/2011; 2011(4):272193. DOI:10.1155/2011/272193
Show more