Johannes Stein

Purpose: Investigation of Microtubuli-associated Protein 2 (MAP2) expression and its clinical relevance in prostate cancer. Material and Methods: MAP2 expression was immunohistochemically analysed on radical prostatectomy specimens using whole block sections (n = 107) and tissue microarrays (TMA; n = 310). The staining intensity was evaluated for carcinoma, benign tissue and prostatic intraepithelial neoplasia. Expression data were correlated with clinicopathological parameters and biochemical recurrence-free survival. Additionally, MAP2 protein expression was quantitatively analysed in the serum of histologically confirmed prostate carcinoma patients and the control group using a commercial enzyme-linked immunosorbent assay. Results: MAP2 staining was significantly stronger in neoplastic tissue than in non-neoplastic prostatic glands, both in whole block sections (p < 0.01) and in TMA sections (p < 0.05). TMA data revealed significantly stronger MAP2 staining in high-grade tumors. Survival analysis showed a significant correlation between strong MAP2 staining in carcinoma and shortened biochemical recurrence-free survival after prostatectomy (p < 0.001). Multivariate Cox regression analysis confirmed MAP2 as an independent predictor for an unfavourable course. Mean MAP2 serum levels for non-PCA vs. PCA patients differed significantly (non-PCA = 164.7 pg/ml vs. PCA = 242.5 pg/ml, p < 0.001). Conclusion: The present data support MAP2 as a novel biomarker in PCA specimens. MAP2 is correlated with tumor grade and MAP2 high-expressing PCA is associated with an increased risk of biochemical recurrence after radical prostatectomy. Future studies are necessary to evaluate MAP2 as a valuable immunohistochemical biomarker in preoperative PCA diagnostic procedures, in particular with regard to treatment modalities.

Introduction: Ring finger proteins play pivotal roles in diverse cellular processes and are implicated in contribution to cancer. Ring finger protein 34 (RNF34) has antiapoptotic and oncogenic properties. RNF34 is upregulated during carcinogenesis and tumor progression in the colorectal adenoma -carcinoma sequence and was already described to mediate chemoresistance. In clear cell renal cell carcinoma (ccRCC), however, the role and expression patterns of RNF34 are unknown. Methods: First, we investigated the association of RNF34 mRNA expression with clinicopathological parameters and survival using data obtained from The Cancer Genome Atlas (TCGA) ccRCC cohort (N = 533). To assess RNA34 protein expression, we performed immunohistochemical (IHC) staining of an established ccRCC cohort (University of Bonn) in a tissue microarray (TMA) format. This validation cohort contains 109 primary ccRCC samples. IHC data were associated with clinicopathological parameters and overall survival (Kaplan -Meier analysis). Adjustment for covariables was done using the Cox regression model. Results: RNF34 expression is correlated with adverse clinicopathological parameters. Survival analysis revealed an association between RNF34 expression and shortened survival. Cox regression analysis confirmed RNF34 expression as an independent prognostic parameter. Conclusion: Our study provides evidence for RNF34 as a prognostic biomarker in ccRCC and points toward a major role of this protein in renal cell carcinoma carcinogenesis.

Background: F-box/SPRY domain-containing protein 1 (FBXO45) plays a crucial role in the regulation of apoptosis via the ubiquitylation and degradation of specific targets. Recent studies indicate the prognostic potential of FBXO45 in several cancers. However, its specific role in prostate carcinoma remains unclear. Methods: A systematic analysis of FBXO45 mRNA expression in PCA was performed using The Cancer Genome Atlas database and a publicly available Gene Expression Omnibus progression PCA cohort. Subsequently, FBXO45 protein expression was assessed via immunohistochemical analysis of a comprehensive tissue microarray cohort. The expression data were correlated with the clinicopathological parameters and biochemical-free survival. The immunohistochemical analyses were stratified according to the TMPRSS2–ERG rearrangement status. To assess the impact of FBXO45 knockdown on the tumour proliferation capacity of cells and metastatic potential, transfection with antisense-oligonucleotides was conducted within a cell culture model. Results: FBXO45 mRNA expression was associated with adverse clinicopathological parameters in the TCGA cohort and was enhanced throughout progression to distant metastasis. FBXO45 was associated with shortened biochemical-free survival, which was pronounced for the TMPRSS2–ERG-positive tumours. In vitro, FBXO45 knockdown led to a significant reduction in migration capacity in the PC3, DU145 and LNCaP cell cultures. Conclusions: Comprehensive expression analysis and functional data suggest FBXO45 as a prognostic biomarker in PCA.

Neurogenic lower urinary tract dysfunction (NLUTD) in asymptomatic patients with MS has been described in preliminary studies, but specific investigations of this topic are rare. Many authors advise early diagnosis and treatment of NLUTD in patients with MS. In contrast, clinical practice and different guidelines recommend neuro-urological diagnostics only in the presence of symptoms. Our aim was to investigate the characteristics of NLUTD and the correlations of clinical parameters with NLUTD in asymptomatic patients with MS. We evaluated bladder diaries, urodynamic findings, and therapy proposals. Correlations of the voided volume, voiding frequency, urinary tract infections, and uroflowmetry including post-void residual with the urodynamic findings were determined. In our study, 26% of the patients were asymptomatic. Of these, 73.7% had urodynamic findings indicative of NLUTD, 21.1% had detrusor overactivity, 13.2% had detrusor underactivity, 13.2% detrusor overactivity and detrusor sphincter dyssynergia, and 57.9% had radiologically abnormal findings of the bladder. No patients presented low bladder compliance or renal reflux. Clinical parameters from the bladder diary and urinary tract infections were found to be correlated with NLUTD, and the absence of symptoms did not exclude NLUTD in patients with MS. We observed that urinary tract damage is already present in a relevant proportion. Based on our results, we recommend that patients with MS be screened for NLUTD regardless of the subjective presence of urinary symptoms or the disease stage.

Purpose: Additive systematic biopsy (SB) contributes to prostate cancer (PCA) detection in MRI-targeted biopsy (TB). However, the reasons for this are not yet clear. We compared the performance of TB, SB and the combined approach (CB) in biopsy-naive men to determine the added value of SB for tumor grading and spatial tumor distribution. Methods: Two hundred and fifty-nine men with PI-RADS 3–5 graded lesions who underwent CB were enrolled. Data were prospectively collected, and cancer detection rates (CDR) were compared at patient and lesion level. Gleason grade up- and down-grading from biopsy to prostatectomy specimens (n = 56; 21.6%) were determined. Clinically significant cancer (csPCA) was defined as Gleason grade ≥ 2. Results: CDR by CB based on PI-RADS categories 3, 4 and 5 for PCA were 24%, 72% and 98% and 17%, 64% and 96% for csPCA. CB detected more PCA and csPCA than TB (p < 0.001). However, TB showed higher efficiency, defined as CDR per biopsy core, for PCA and csPCA in PI-RADS 4–5 rated patients (p < 0.001). Concordance between biopsy and prostatectomy grading was highest in CB with misdiagnosis of csPCA in 25% of men. TB missed cancer attributed to the index lesion in 10.2% and underestimated csPCA in 7%. In these cases, 76% of csPCA were detected and 85% were upgraded to csPCA by SB in adjacent sectors. Conclusion: SB cannot be safely abundant without increased diagnostic uncertainty. When TB missed csPCA, SB detected it close to the MRI-target lesion. Therefore, perifocal biopsies could potentially replace 12-core SB with increased efficiency in taking manageable risks.

Technological progress is continuously improving medical care. The urological profession is well-known for further development of technical innovations and quick transfer into daily practice. Robot-assisted surgery, for example, has been part of the clinical routine in modern urological clinics for many years. In the endourological field, the implementation and further evolution of laser-based procedures have dominated research in the last decade. Recently, in 2015, the presentation of a new robot-assisted technique of waterjet-based ablation of prostate tissue raised attention in the society—the AquablationVR therapy. Aquablation therapy has been investigated within several randomized and controlled clinical trials, and—with growing experience— the technique has been modified over recent years to improve the safety of the procedure. Due to the clinical outcome, the number of hospitals performing Aquablation therapy is increasing continuously. This article provides an overview of the technique, its modifications, and the current status of evidence. Cite this article as: Stein J, Cox A, Hauser S, Ritter M, Bach T. Evolution of AquablationVR—From innovation to establishment. Turk J Urol. 2021; 47(5): 351-357.

Purpose: Low-dose computer tomography (NCCT) is the standard imaging modality for patients with acute flank pain with a suspicion of urolithiasis. The stone size is usually measured 2D by a radiologist. We compared 3D stone measurement using different windows to the 2D measurement and evaluated the clinical impact on ureterorenoscopic stone removal (URS). Methods: One hundred sixty-four patients (201 stones) with a preoperative NCCT, following a URS within 4 weeks, were included in this study. Stone location, number and size of stones, operating time, and laser lithotripsy were documented. Stones were measured in 3D using bone and soft tissue window. The maximum diameter was compared to the radiological report. The U test, Kruskal-Wallis, and regression were used for statistical analyses. Results: Almost two-thirds (64.68%; 130 stones) of stone measurements in 3D with the bone window were lower than the radiologist reports in 2D. One-third (34.83%; 70 stones) of stone measurements were higher and 0.5% (1 stone) reported the same size. Using the 3D soft tissue window, 81.09% (163 stones), 17.91% (37 stones), and 1% (2 stones) of stones were measured bigger, smaller, or had the same measurement results, respectively. In the clinical setting, we could calculate a cutoff for laser lithotripsy at a maximum stone diameter of 5.70 mm (p < 0.01) with the 3D and 6.01 mm with the 2D measurements, respectively, and found a significant correlation between maximum stone diameter and operating time (p < 0.01) and number of stones and operating time (p < 0.01 with and p = 0.02 without laser). Conclusion: 3D stone measurement with bone window seems to be more accurate than 2D measurement, but 2D is sufficient for planning stone treatment.

Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods: DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.

Objective: To analyze the expression of mitochondrial respiratory chain protein subunits in clear cell renal cell carcinoma.Methods: Possible prognostic candidates were determined using The Cancer Genome Atlas database (n = 605). The database provided valid messenger ribonucleic acid expression data for 93 genes encoding for the subunits. Selected subunits were further investigated at the messenger ribonucleic acid and protein level by real‐time polymerase chain reaction, western blot and immunohistochemistry with the cohorts of the University Hospital Bonn.Results: The Cancer Genome Atlas messenger ribonucleic acid expression data indicated univariate and multivariate prognostic impact for seven subunits (NDUFS8, NDUFS7, COX5B, COX6B1, SDHD, COX15 and COX19). Using real‐time polymerase chain reaction, significant downregulation (P < 0.05, n = 74) could be shown for COX5B, COX6B1, NDUFS7 and NDUF8 in clear cell renal cell carcinoma tissue. Survival analysis of polymerase chain reaction data showed a non‐significant relationship (P = 0.067) of high COX5B expression and poor overall survival. Western blot (n = 8) and immunohistochemistry analysis (n = 167) confirmed significant COX5B downregulation on the protein level. Immunohistochemistry analysis identified COX5B as a prognostic marker for overall (P = 0.017) and cancer‐specific survival (P = 0.042).Conclusions: The present study findings suggest downregulation of additional subunits of mitochondrial respiratory chain proteins in clear cell renal cell carcinoma. Remarkably, COX5B, a subunit of the respiratory chain complex IV, can be identified as a novel prognostic marker.