<i>PTEN</i> Loss with <i>ERG</i> Negative Status is Associated with Lethal Disease after Radical Prostatectomy.

Abstract

Few groups have investigated the combined effects of <i>PTEN</i> loss and <i>ERG</i> expression on the outcomes of metastasis of or death from prostate cancer in surgically treated patients. We examined the association of <i>PTEN/ERG</i> status with lethal prostate cancer in patients treated with radical prostatectomy. Included in analysis were 791 patients with clinically localized prostate cancer treated with radical prostatectomy at a single institution. Genetically validated immunohistochemistry assays for <i>PTEN</i> and <i>ERG</i> were performed on tissue microarrays. Multivariable Cox proportional hazard models were used to assess the association of <i>PTEN/ERG</i> status with lethal prostate cancer (defined as metastasis or prostate cancer specific death), adjusting for patient age, race, pathological grade and stage, and surgical margin status. Median followup in the cohort was 12.8 years. Of 791 cases 203 (25%) demonstrated <i>PTEN</i> loss and 330 of 776 (43%) were <i>ERG</i> positive. On multivariable analysis <i>PTEN</i> loss (HR 1.9, 95% CI 1.2-3.0, p=0.012) but not <i>ERG</i> expression (HR 0.6, 95% CI 0.4-1.1, p=0.11) was associated with an increased risk of lethal prostate cancer. The association of <i>PTEN</i> loss with lethal disease only remained among men with <i>ERG</i> negative tumors (HR 2.3, 95% CI 1.3-4.1, p=0.005) and not <i>ERG</i> positive tumors (HR 1.1, 95% CI 0.6-2.1, p=0.81). <i>PTEN</i> loss is associated with an increased risk of lethal prostate cancer after radical prostatectomy and this risk is most pronounced in the subgroup of patients with <i>ERG</i> negative tumors. This work corroborates the use of <i>PTEN</i> and <i>ERG</i> status for risk stratification in surgically treated patients.