Correlation of UHRF1 expression in primary prostate cancer patients with adverse prognosis

Background: Cancer of the prostate is a leading cause of cancer death in western countries. There is a great need to understand the clinical course of the disease and to distinguish the indolent tumors from those with aggressive behavior. Epigenetic mechanisms play an essential role in cancer initiation and progression. Our groups have recently provided evidence that over-expression of UHFR1 (ubiquitin-like with PHD and ring finger domain) leads to prostate cancer progression by activating a robust epigenetic switch involving silencing of a network of tumor suppressor genes. The purpose of this study was to evaluate in a clinical setting the prognostic impact of UHFR1 expression. Methods: In a series of 225 eligible patients (median age 63 years, range 44-75) with prostate cancer treated in a single institution with prostatectomy between 1990 and 1999 we evaluated the tumor nuclear expression of UHRF1 by immunohistochemistry (IHC). Clinical and histological data of the series were also reviewed. The UHFR1 expression (evaluated in tissue microarrays by immunohistochemistry) and prognostic factors were analyzed using univariate analyses and multivariate logistic regression analysis to identify association with overall survival (OS). Results: The median FU for the series was 137 months (range 1-229), eighty-one patients died (median FU 85 months). In Ninety-seven patients (43%) the UHRF1 expression was positive. In univariate analyses Gleason Score (<7 vs 7-9), Stage Risk Group (TNM Stage <III vs Stage III and/or N+) and UHFR1 expression (negative vs positive) were significant prognostic factors for OS with p-value <0.0001. In multivariate analyses Gleason Score, Stage Risk Group and UHFR1 expression were independent predictors for OS with respectively HRs of 2.77 (95% CI 1.72-4.46) p<0.0001, HRs of 1.96 (95% CI 1.14-3.37) p=0.014 and Hrs 1.35 (95% CI 1.02-1.78) p=0.030. Conclusions: Our results indicate that expression of UHFR1 protein, independently from historical prognostic factors, is linked with adverse prognosis for overall survival in a homogeneous primary prostate cancer treated group with long-term follow-up.