Role of ERG, PTEN and KI67 Proteins Expression in Prognosis of Metastatic Prostate Cancer

Background: Prostate cancer is a leading cause of cancer-related mortality in men. Despite improvements in early detection of prostate cancer as a result of PSA screening, we still lack molecular markers to effectively distinguish patients with high risk of disease progression from the indolent majority. Aim of the work: To assess the prognostic value of ERG, PTEN and KI67 proteins expression in metastatic prostate cancer patients, as well as their relationship to clinicopathologic features of the disease. Patients and Methods: ERG, PTEN and KI67 proteins expression was assessed immunohistochemically in series of metastatic prostate cancers and their prognostic significance was evaluated. Results: High ERG score as well as high KI67 labeling index (LI) were strongly associated (P <0.001) with high pre-treatment PSA level, Gleason score ?7, advanced tumor stage, metastasis affecting both bone & lymph nodes and biochemical progression. PTEN loss was significantly associated with high pre-treatment PSA level (P ?0.001), Gleason score ?7 (P =0.002), advanced tumor stage (P =0.015), metastasis affecting both bone & lymph nodes (P =0.002) and biochemical progression (P =0.001). A significant association was found between higher KI67 LI (P ?0.001), higher ERG expression score (P =0.005) & PTEN loss (P =0.007) and shorter progression free survival. ERG expression and PTEN loss were significantly associated with KI67 LI (P =0.011 & 0.0.013 respectively), however, no relationship could be proved between both of them (P =0.256). ERG (P =0.025) was the only independent predictor for biochemical progression in multivariate analysis. Conclusions: ERG and KI67 expressions and PTEN loss have an important prognostic value in metastatic prostate cancer. Using them to differentiate between patients who are at a high or low risk of disease progression may help to identify patients who will benefit the most from treatment.