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

Background The goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence. Patients and methods Study was conducted on a retrospective cohort of 123 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-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease. Results After follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and 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 frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068). Conclusions Cytoplasmic expression of NF-κB is associated with more biochemical progression 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.

TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer.

BACKGROUND: TMPRSS2:ERG gene aberration may be a novel marker that improves risk stratification of prostate cancer before definitive cancer therapy, but studies have been inconclusive. METHODS: The study cohort consisted of 202 operable prostate cancer Slovenian patients who underwent laparoscopic radical prostatectomy. We retrospectively constructed tissue microarrays of their prostatic specimens for fluorescence in situ hybridization, with appropriate signals obtained in 148 patients for subsequent statistical analyses. RESULTS: The following genetic aberrations were found: TMPRSS2:ERG fusion, TMPRSS2 split (a non-ERG translocation) and ERG split (an ERG translocation without involvement of TMPRSS2). TMPRSS2:ERG gene fusion happened in 63 patients (42 %), TMPRSS2 split in 12 patients and ERG split in 8 patients. Association was tested between TMPRSS2:ERG gene fusion and several clinicopathological variables, i.e., pT stage, extended lymph node dissection status, and Gleason score, correcting for multiple comparisons. Only the association with pT stage was significant at p = 0.05: Of 62 patients with pT3 stage, 34 (55 %) had TMPRSS2:ERG gene fusion. In pT3 stage patients, stronger (but not significant) association between eLND status and TMPRSS2:ERG gene fusion was detected. We detected TMPRSS2:ERG gene fusion in 64 % of the pT3 stage patients where we did not perform an extended lymph node dissection. CONCLUSIONS: Our results indicate that it is possible to predict pT3 stage at final histology from TMPRSS2:ERG gene fusion at initial core needle biopsy. FISH determination of TMPRSS2:ERG gene fusion may be particularly useful for patients scheduled to undergo a radical prostatectomy in order to improve oncological and functional results.

Staging of prostate cancer: a review with reference for further refinement.

Staging of prostate carcinoma provides a standardized method for tumor classification which is based on involvement of the prostate gland, adjacent local structures, regional lymph nodes, and distant sites. Staging information is therefore crucial for clinicians to be able to assess risk of disease progression, to offer therapeutic choices in the individual patient, and to provide population-based prognostic information. Clinical staging, which is based on data obtained prior to first definitive treatment, relies on tumor determination by digital rectal examination, transrectal ultrasonography, other imaging techniques, and serum PSA level, while pathological staging requires histological identification of tumor extent in prostate gland and surrounding tissues. T1 tumors, denoted to clinically unapparent, not palpable or visible by imaging, are diagnosed by transurethral resection of the prostate procedure or needle biopsy. T2 tumors are confined to the organ, are subdivided by involvement in one or both lobes, and are determined by radical prostatectomy procedure. Stage T3 denotes locally advanced tumors that spread beyond the organ's boundaries, and T4 denotes invasion or fixation to the pelvic organs. Despite wide acceptance of the system as a whole, the current 2010 revision of the American Joint Committee on Cancer/Union for International Cancer Control tumor, node and metastasis (TNM 7) appears to contain some controversies, particularly T2 three-tiered subclassification. This review will cover suggested changes to further TNM editions; these changes have been accumulated in the literature in recent years and include items such as lymph node involvement quantification, "vanishing" carcinoma, Gleason score, resection margin status, pretreatment serum PSA level, as well as difficulties the pathologist may encounter in microscopic examination which may hamper accurate stage assessment.