Significance of nuclear factor kappa beta activation on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolence

Background. Prostate cancer (PCa) is the most common cancer in men in developed European countries. Majority of men newly diagnosed with PCa are candidates for primary curative therapy, either with radical prostatectomy (RP) or radiation. However, many PCa are low risk, even indolent and these patients are candidates for active surveillance, so the prediction of such cancers is needed to avoid overtreatment. The main goal of our study was to find out whether the immunohistochemical expression of NF-κB p65 in biopsy samples with Gleason score 3+3=6 (GS 6) can be a negative predictive factor for PCa indolence. Methods. Study was based on a retrospective cohort of 178 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κβ p65. Both cytoplasmatic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression (BP) of disease. The final analysis involved 123 patients regarding the postoperative stage, surgical margins and GS and 118 regarding the BP. Results. Postoperative pathological stage 3 was noticed in 27 (22%) and positive surgical margins were detected in 13 patients (10,6%). After median follow-up of 66 months, BP (PSA ≥ 0,05 ng/ml) occurred in 20 (16,9%) patients, 11 (55%) with GS 6 after RP and 9 (45%) with GS 7. Cytoplasmatic nor nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more BP compared to those with negative cytoplasmic NF-kB reaction with PSA 0,2 ng/ml as cutoff point (p=0,015) and a trend towards more BP with PSA ≥ 0,05 ng/ml as cutoff point (p=0,068). Conclusions. Cytoplasmic expression of NF-κB is associated with more BP and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.