RIPK2 as a prognostic biomarker and predictor of aggressive prostate cancer.

211 Background: Receptor-Interacting Protein Kinase 2 (RIPK2) has been known to play a significant role in inflammation and anti-microbial response via the NF-KB pathway. Recently, RIPK2 was also shown to stabilize and activate c-Myc, a molecule implicated in the progression of various malignancies including prostate cancer (PCa). Our study aims to determine the prognostic value of RIPK2 expression in PCa using immunohistochemistry (IHC) analysis of biopsy specimens with special focus on a predominantly African American (AA) cohort. Methods: Eligible patients aged ≥18 years diagnosed with PCa at the Washington DC VA Medical Center were randomly selected and retrospectively grouped into indolent, locally advanced, and metastatic disease categories and stratified by age, ethnicity, AJCC stage, PSA and Gleason score at diagnosis. Representative tissue from prostate core biopsy, transurethral resection, or radical prostatectomy was analyzed for each patient. RIPK2 expression and intensity were assessed by IHC and graded by two independent pathologists by the following scale: 0 (no cytoplasmic staining), 1+ (weak cytoplasmic staining similar to benign prostatic tissue), 2+ (moderate cytoplasmic staining), and 3+ (strong cytoplasmic staining). The primary endpoint was RIPK2 expression by disease group, and key secondary outcomes were RIPK2 association with Gleason score, PSA at diagnosis, age and race. Fisher’s exact test was used to evaluate statistical significance of the association between RIPK2 expression level and disease category. Results: A total of 89 patients were selected for analysis, of which 75 (84.3%) were AA. All tumors had at least 1+ level RIPK2 expression and there was a highly significant difference in RIPK2 expression according to disease severity (p < 0.001). Stratified RIPK2 expression was 1.53, 1.83, and 2.28 in the indolent, locally advanced, and metastatic groups respectively. We observed a significant directly proportional correlation between RIPK2 expression and a higher PSA level (p= 0.0021), Gleason score (p< 0.001), higher age (p= 0.0276), and AJCC stage (p< 0.001) at the time of diagnosis. Mean RIPK2 expression was 1.81 in AA patients and 2.15 in White patients (p= 0.0332). Conclusions: PCa is the most prevalent cancer in US males and there is an urgent need for more accurate biomarkers that can predict disease severity and suggest actionable targeted therapy. In this retrospective analysis, we confirm that higher RIPK2 expression is associated with more advanced PCa. We extend these findings to a predominantly AA cohort, which may promote improvements in personalized medicine for this population at higher risk for PCa if RIPK2-targeting drugs such as Ponatinib can be utilized.