Collapsin response mediator protein 4 promotor methylation level as a potential predictor for diagnosing primary malignant lymphoma of the prostate.

BACKGROUND: Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. METHODS: We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (-) (10 cases)] and also to metastatic prostate adenocarcinoma (mPCa) and its positive lymph node tissue [mPCa-LN (+) (10 cases)]. Methylation of the CRMP4 promotor in each group was analyzed statistically. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CRMP4 methylation in PMLP. RESULTS: The average methylation value of CRMP4 in 10 PMLP patients, 20 cases of prostate adenocarcinoma tissue, 10 cases LPCa-LN (-) and 10 cases mPCa-LN (+) were 42.3, 30.6, 6.7 and 20.3%, respectively. A Kruskal-Wallis test showed that the difference of CRMP4 methylation was significant (X2 = 38.0, P < 0.001). An ROC curve analysis found that CRMP4 methylation > 40.9% could diagnose PMLP. This method had 90% sensitivity and 95% specificity under conditions of CRMP4 methylation > 40.9%. The area under the curve (AUC) was 0.957. CONCLUSIONS: Methylation of the CRMP4 gene was significantly increased in PMLP, and it is expected to become a new predictor for PMLP.

Coexpression of TLR9 and VEGF-C is associated with lymphatic metastasis in prostate cancer.

Prostate cancer (PCa) is one of the most frequent cancers in men, and its biomolecular targets have been extensively studied. This study aimed to analyze the expression of toll-like receptor 9 (TLR9) and vascular endothelial growth factor C (VEGF-C) and the clinical value of the coexpression of TLR9 and VEGF-C in PCa. We retrospectively evaluated 55 patients with clinically localized, intermediate-risk, or high-risk PCa who underwent laparoscopic radical prostatectomy (LRP) and extended pelvic lymph node dissection (ePLND) without neoadjuvant hormonal therapy at a single institution from June 2013 to December 2016. In all 55 patients, the median number of lymph nodes (LNs) resected was 23 (range: 18-31), and a total of 1269 LNs were removed, of which 78 LNs were positive. Seventeen patients had positive LNs, with a positive rate of 30.9%. In addition, the immunohistochemical results in the above patients revealed that high TLR9 expression was correlated with higher Gleason score (GS) (P = 0.049), increased LN metastasis (P = 0.004), and more perineural invasion (PNI) (P = 0.033). Moreover, VEGF-C expression was associated with GS (P = 0.040), pathological stage (pT stage) (P = 0.022), LN metastasis (P = 0.003), and PNI (P = 0.001). Furthermore, a significant positive correlation between TLR9 and VEGF-C was found (P < 0.001), and the TLR9/VEGF-C phenotype was associated with LN metastasis (P = 0.047). Collectively, we propose that TLR9 stimulation may promote LN metastasis in PCa cells through the upregulation of VEGF-C expression, thereby affecting the prognosis of PCa patients. Therefore, these markers may serve as valuable targets for the treatment of PCa.

Combined analysis of CRMP4 methylation levels and CAPRA-S score predicts metastasis and outcomes in prostate cancer patients.

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.

Laparoscopic Radical Prostatectomy Plus Extended Lymph Node Dissection in Combination With Immediate Androgen Deprivation Therapy for Cases of pT3-4N0-1M0 Prostate Cancer: A Multimodal Study of 8 Years' Follow-up.

PURPOSE: To investigate the functional and oncologic outcomes of patients with locally advanced or lymph node (LN) metastatic prostate cancer (PCa) treated by laparoscopic radical prostatectomy (LRP) with extended lymph node dissection (ePLND). METHODS: From June 2004 to March 2014, a total of 232 cases (pT3-4N0-1M0) including 160 locally advanced PCa and 72 LN metastatic PCa who received immediate androgen deprivation therapy after LRP plus ePLND were enrolled onto our study. The patients were followed up for 12 to 124 months. Surgical records, surgical margin status, complications, urinary continence, and oncologic outcomes were presented. RESULTS: The mean operation time and bleeding were 230 minutes and 105 mL, respectively. The rates of urinary continence were 91.4% and 94.8% at 6 and 12 months, respectively. We observed 122 biochemical recurrent cases. The 5- and 8-year biochemical relapse-free survival rates were 47.3% and 46.7%, respectively. The 5- and 8-year overall and cancer-specific survivals were 81.2%, 80.1%, 90.6%, and 90.6%, respectively. The survival analysis showed that biochemical recurrence-free survival rates were significantly lower for patients with higher Gleason score (77.3% vs. 39.6% vs. 30.8%, P = .003 log rank), higher T stage (55.7% vs. 41.4% vs. 21.4%, P = .039 log rank), positive surgical margin (51.1% vs. 29.3%, P = .000 log rank), and higher CAPRA-S score (68.6% vs. 35.0% vs. 29.2%, P = .000 log rank). There were no significant differences in biochemical relapse-free (40.9% vs. 49.3%, P = .286), overall (75.6% vs. 81.9%, P = .398), and cancer-specific (87.3% vs. 92.1%, P = .284) survival between LN-positive and -negative PCa. CONCLUSION: LRP plus ePLND in combination with immediate androgen deprivation therapy is a feasible approach to patients with pT3-4N0-1M0 PCa; favorable functional and oncologic outcomes were presented postoperatively.

Laparoscopic Radical Prostatectomy after Previous Transurethral Resection of the Prostate in Clinical T1a and T1b Prostate Cancer: A Matched-Pair Analysis.

PURPOSE: To analyze and compare surgical, oncological and functional outcomes of laparoscopic radi­cal prostatectomy (LRP) in patients with and without previous transurethral resection of the prostate (TURP). MATERIALS AND METHODS: In total, 785 men underwent LRP at our institution from January 2002 to December 2012. TURP had been performed previously in 35 of these patients (TURP group). A matched-pair analysis iden­tified 35 additional men without previous TURP who exhibited equivalent clinicopathological characteristics to serve as a control group. Perioperative complications and surgical, functional, and oncological outcomes were compared between the two groups. RESULTS: The groups were similar in age, body mass index, serum prostate-specific antigen level, and pre- and post-operative Gleason scores. Patients in the TURP group had greater blood loss (231 vs. 139 mL), longer opera­tive times (262 vs. 213 min), a greater probability of transfusion (8.6% vs. 0%), and a higher rate of complications (37.1% vs. 11.4%) compared with the control group. The positive surgical margin rate was higher in the TURP group, but this difference was not statistically significant (P = .179). The continence rates at one year after surgery were similar, but a lower continence rate was identified in the TURP group (42.9% vs. 68.6%) at 3 months. Bio­chemical recurrence developed in 17.1% and 11.4% of the patients in the TURP and control groups, respectively, after a mean follow-up of 57.6 months. CONCLUSION: LRP is feasible but challenging after TURP. LRP entails longer operating times, greater blood loss, higher complication rates and worse short-term continence outcomes. However, the radical nature of this cancer surgery is not compromised.