Expression of GP88 (Progranulin) Protein Is an Independent Prognostic Factor in Prostate Cancer Patients

Abstract

Prostate cancer, the second most common cancer, is still a major cause of morbidity and mortality among men worldwide. The expression of the survival and proliferation factor progranulin (GP88) has not yet been comprehensively studied in PCa tumors. The aim of this study was to characterize GP88 protein expression in PCa by immunohistochemistry and to correlate the findings to the clinico-pathological data and prognosis. Immunohistochemical staining for GP88 was performed by TMA with samples from 442 PCa patients using an immunoreactive score (IRS). Altogether, 233 cases (52.7%) with negative GP88 staining (IRS < 2) and 209 cases (47.3%) with positive GP88 staining (IRS ≥ 2) were analyzed. A significant positive correlation was found for the GP88 IRS with the PSA value at prostatectomy and the cytoplasmic cytokeratin 20 IRS, whereas it was negatively associated with follow-up times. The association of GP88 staining with prognosis was further studied by survival analyses (Kaplan–Meier, univariate and multivariate Cox’s regression analysis). Increased GP88 protein expression appeared as an independent prognostic factor for overall, disease-specific and relapse-free survival in all PCa patients. Interestingly, in the subgroup of younger PCa patients (≤65 years), GP88 positivity was associated with a 3.8-fold (p = 0.004), a 6.0-fold (p = 0.008) and a 3.7-fold (p = 0.003) increased risk for death, disease-specific death and occurrence of a relapse, respectively. In the PCa subgroup with negative CK20 staining, GP88 positivity was associated with a 1.8-fold (p = 0.018) and a 2.8-fold increased risk for death and disease-specific death (p = 0.028). Altogether, GP88 protein positivity appears to be an independent prognostic factor for PCa patients.