Detection of xenotropic murine leukemia virus-related virus in normal and tumor tissue of patients from the southern United States with prostate cancer is dependent on specific polymerase chain reaction conditions

Abstract

Background: There are questions regarding the prevalence of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and its association with the RNASEL R462Q polymorphism. We therefore investigated whether XMRV infection could be found in patients with prostate cancer from the southern United States, and we sought to verify the association with the R462Q.

Methods: Prostate tissue specimens of 144 patients with prostate cancer from the southern United States were genotyped for R462Q by real time polymerase chain reaction allelic discrimination and were screened for XMRV proviral DNA by nested polymerase chain reaction specific for the env gene.

Results: The R462Q polymorphism was found at an allelic frequency of 0.33. XMRV was detected in 32 (22%) of the 144 patients. Patients were significantly more likely to test positive for XMRV in both tumor and normal tissue rather than either alone (κ = 0.64). A positive result for XMRV was not significantly correlated with the R462Q polymorphism (P = .82) or clinical pathological parameters of prostate cancer, including Gleason score (P = .29).

Conclusions: XMRV is detectable in normal and tumor prostate tissue from patients with prostate cancer, independent of R462Q. The presence of XMRV in normal tissue suggests that infection may precede cancer onset.

Figure 1

Sequence analysis of patient-derived PCR products. A, Comparison of the predicted Env protein sequences from the PCR products of 17 patients with the Env sequence of the XMRV clone VP62; variable regions (VR) A, B, and C are indicated; dots indicate identical residues; and a stop codon is indicated by an asterisk. B, Phylogenetic tree of the XMRV patient clones compared with other murine retroviruses.

Figure 2

Distribution of XMRV between normal and cancer tissue of 57 PCA patients. The white circle represents patients from whom XMRV DNA was detected by PCR in normal tissue, the dark gray circle represents patients from whom XMRV DNA was detected by PCR in tumor tissue, and the light gray overlap represents patients from whom both tissue types tested positive for XMRV DNA. Twenty-nine of the 57 patients tested negative for XMRV DNA. Patients were found to be more likely to test positive for both tissue types (simple kappa coefficient = 0.64).

Figure 3

XMRV infection is not significantly correlated with Gleason score. Numbers of infected patients (light gray) and uninfected patients (dark gray) are graphed according to Gleason score. No association between provirus positivity and Gleason score was found (Fisher’s exact test, p = 0.29; two sample t-test, p = 0.30).