Clinical utility of assessing PTEN and ERG protein expression in prostate cancer patients: a proposed method for risk stratification

Objectives: To assess the prognostic value of ERG and PTEN protein expression as two of the most common genetic aberration in men with prostate cancer managed non-surgically by androgen deprivation therapy (ADT). Materials and methods: 463 tumor samples were assessed by double immunohistochemistry stains for ERG and PTEN and data correlated with clinical pathological features including, Gleason score, patients’ outcome and ADT. Results: ERG expression and PTEN protein loss were present in 28.2% and 38% of total patients respectively. There was a significant interplay between ERG and PTEN expression with 21.8% PTEN negative tumors being ERG positive (p < 0.001). Both ERG and PTEN showed significant association with lethal disease in all patients and those treated with prior ADT representing castrate-resistant disease. However, only PTEN remained significant in multivariable proportional hazards regression analysis, when including Gleason score and patients’ age. Depending on patient’s subgroup, intact positive PTEN intensity showed better cancer-specific survival with HR ranging from 0.25 to 0.4 compared to tumors with loss of PTEN expression. Assessing combined marker status, patients with decreased PTEN intensity without ERG positivity showed the worst clinical outcome compared to those with no PTEN loss and no ERG expression, where they had best clinical outcome. Patients with ERG expression with or without PTEN loss showed intermediate risk in relation to lethal disease. Conclusion: This study confirms a significant prognostic role for assessing ERG and PTEN in men with prostate cancer. It supports a role for utilizing combined ERG/PTEN status clinically and prospectively for stratifying PCa patients into different prognostic groups.