Human Endogenous Retrovirus K Expression As A Possible Adjunct To Psa In The Diagnosis Of Prostate Cancer

Embedded in the genomes of nearly all vertebrates, are sequences of retroviral origin. These endogenous retroviruses (ERVs) are the result of ancient retroviral infections of the germline. 8% of the human genome consists of such sequences (HERVs).To date, no active, infectious HERV has been observed in humans, but high levels of retroviral mRNA and protein from a group known as HERV-K (HML-2) have been observed in some human cancers. Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate commonly diagnosed in older men. Its prevalence negatively impacts on the sensitivity of PSA scores. We previously reported an association between high levels of HERV-K (HML-2) gag mRNA expression and a prostate cancer diagnosis (Wallace et al., 2014). The strength of this association increased with age. We hypothesised that measuring HERV-K (HML-2) expression could improve the discriminatory ability of PSA in the diagnosis of prostate cancer versus BPH. We set out to analyse differences in HERV-K (HML-2) protein expression between prostate adenocarcinoma and BPH. To this end, we conducted immunohistochemistry on prostate tissue microarrays (LS-SPRCA26, LS-SCA19; LifeSpan Biosciences) containing cores from prostate adenocarcinoma and BPH cases. TMAs were stained with an anti-HERV-K gag antibody (LS-C65287, LifeSpan Biosciences) and scored by an independent pathologist. We observed significantly greater epithelial HERV-K gag protein expression in BPH cores versus prostate adenocarcinoma cores (Fisher exact test, p = 0.001). Similar differences were also observed in stromal tissue (Fisher exact text, p = 0.02). Significant differences were also seen after positive expression levels were dichotomized into high versus low subgroups for both epithelial tissue (Fisher exact test, p = 0.001) and for stromal tissue (Fisher exact test, p = 0.034). Finally, we considered an association between HERV-K gag protein expression levels and tumor stage, but we did not observe any significant differences. Our data indicate that measuring HERV-K (HML-2) expression may improve the discriminatory ability of PSA in the diagnosis of prostate cancer versus BPH and that its potential utility as an adjunct biomarker warrants further investigation. Furthermore, increased sample size in relation to tumor stage will enable its prognostic potential to be evaluated. Citation Format: Ronan Downey, Laura Murillo, Teresa McHale, Tiffany Wallace, Caleb Seufert, Aaron Schetter, Tiffany Dorsey, Carol Johnson, Radoslav Goldman, Christopher Loffredo, Peisha Yan, Francis Sullivan, Francis Giles, Feng Wang-Johanning, Stefan Ambs, Sharon Glynn. Human endogenous retrovirus K expression as a possible adjunct to PSA in the diagnosis of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 536. doi:10.1158/1538-7445.AM2015-536