Differences in the expression of PTP-1B phosphatase in prostate cancer (PC) patients with and without adverse pathologic features (APF).

Abstract

e16543 Background: Localized PC is a heterogeneous disease. Currently, clinical markers are insufficient to predict the presence of APF before prostatectomy. PTP-1B phosphatase is implicated in insulin/leptin receptor activity and in cancer cells migration and invasion. PTP-1B could be a predictor marker of APF in PC. The aim was to compare the expression of PTP-1B in PC patients with vs without APF. The secondary aim was to evaluate PTP-1B as an independent predictive factor. Methods: Radical prostatectomy samples of patients with localized PC performed in a single center were identified (1990-2015). Pathologic features were re-evaluated by an expert pathologist. APF was defined as: seminal vesicle invasion or extra-capsular invasion or positive surgical margins. Tissue microarrays (TMA) immunohistochemistry for PTP-1B was done and evaluated in a 0-9 score. Statistics: Mann Whitney U-test was used to compare variables, and Spearman´s rho for correlation. To evaluate the association of PTP-1B score with the outcome of APF, a logistic regression analysis with two models was performed. The first, included biologically associated variables (metformin use, T2DM), and the second, stablished risk factors (PSA, Gleason score (GS)). Results: We identified 352 PC cases. In 190 a TMA was done, and 73 were optimal for PTP-1B expression evaluation and were included for analysis. Patient´s mean age was 62 ± 7 yo. Twenty nine (40%) without APF, and 44 (60%) with APF. Median PTP-1B score was 5 [3-8] in patients without APF vs 8 [5-9] in patients with APF (p = 0.026). PTP-1B score correlated with GS (r = 0.24, p = 0.042) and PSA (r = 0.24, p = 0.046). PTP-1B was a risk factor for the presence of APF even adjusted for the presence of metformin use and T2DM (OR 1.21; 95% CI 1.01-1.45; p = 0.037). However, PTP-1B score was not an independent risk factor for APF when PSA and GS were included (OR 1.68; 95% CI 0.97-1.41; p = 0.11). The addition of PTP-1B score to the prediction model for APF, which includes GS and PSA, only provided a slight increase in accuracy (AUC 0.73; 95% CI 0.61-0.84 vs AUC 0.71; 95% CI 0.59-0.82). Conclusions: Patients with PC and APF have an increased expression of PTP-1B.