MicroRNAs (miRs) are involved in the pathogenesis of several neoplasms; however, there are no data on their expression patterns and possible roles in adrenocortical tumors. Our objective was to study adrenocortical tumors by an integrative bioinformatics analysis involving miR and transcriptomics profiling, pathway analysis, and a novel, tissue-specific miR target prediction approach. Thirty-six tissue samples including normal adrenocortical tissues, benign adenomas, and adrenocortical carcinomas (ACC) were studied by simultaneous miR and mRNA profiling. A novel data-processing software was used to identify all predicted miR-mRNA interactions retrieved from PicTar, TargetScan, and miRBase. Tissue-specific target prediction was achieved by filtering out mRNAs with undetectable expression and searching for mRNA targets with inverse expression alterations as their regulatory miRs. Target sets and significant microarray data were subjected to Ingenuity Pathway Analysis. Six miRs with significantly different expression were found. miR-184 and miR-503 showed significantly higher, whereas miR-511 and miR-214 showed significantly lower expression in ACCs than in other groups. Expression of miR-210 was significantly lower in cortisol-secreting adenomas than in ACCs. By calculating the difference between dCT miR-511 and dCT miR-503 (delta cycle threshold), ACCs could be distinguished from benign adenomas with high sensitivity and specificity. Pathway analysis revealed the possible involvement of G2/M checkpoint damage in ACC pathogenesis. To our knowledge, this is the first report describing miR expression patterns and pathway analysis in sporadic adrenocortical tumors. miR biomarkers may be helpful for the diagnosis of adrenocortical malignancy. This tissue-specific target prediction approach may be used in other tumors too.

The accumulation of genetic alterations plays a role in the evolution of bladder cancer. These changes can be detected in the urine by DNA analysis of the cells exfoliated from the bladder wall enabling us to detect bladder cancer. The urine supernatant, besides the urine sediment, contains DNA, however in a much smaller amount. The origin of DNA in these two fractions is probably different. Our aim was to evaluate which fraction (supernatant or sediment) provides more reliable results in detecting tumors. We analyzed blood, urine and tumor samples taken from 80 individuals (44 patients with bladder cancer, 20 control patients and 16 healthy volunteers) by using 12 microsatellite markers mapped on 6 chromosomes. Microsatellite alterations were detected in the urine sediment and supernatant in 86% of the cancer cases. Urine sediment alone had a sensitivity of 68%, while urine supernatant alone indicated aberrations in 80% of the tumors. In the superficial (Ta/T1) cases, a considerable difference in sensitivity, 84 vs. 67%, was found between the two fractions in favor of urine supernatant. We also detected deletions in the control groups, although in a much lower proportion. Loss of the 16q24 chromosomal region showed a significant correlation with tumor stage (p=0.02). Microsatellite analysis of the urine is an efficient and noninvasive molecular method to detect bladder cancer. The analysis of free DNA in the urine supernatant provides a higher detection rate. The marker on the chromosomal region 16q24 is suggested to have a prognostic value.

Introduction: Our aim was to identify the independent risk factors associated with urinary incontinence after radical retropubic prostatectomy (RRP). Materials and Methods: Using univariate and multivariate analyses, we examined several pre- and perioperative factors. One hundred and sixty-six patients were divided into three groups: patients who were immediately continent after catheter removal (group I), patients who became continent later (group II) and incontinent patients (group III). Results: There were 34 patients (20.5%) in group I, 111 (66.9%) in group II, and 21 (12.6%) in group III. The multivariate analysis between the continent and incontinent patients proved that the postoperatively measured total length of the posterior urethra (strongly associated with length of the sphincter, length of the urethral stump and the presence of anastomotic stricture) was the independent risk factor for permanent incontinence or delayed continence following RRP. The age of patients per se represented a risk factor only for delayed continence, but not for permanent incontinence. Conclusions: Postoperatively measured shorter posterior urethral length results in an increased risk of urinary incontinence and delays continence after RRP. It seems that older age only delays reaching continence.

Tissue protein expression of IMP3 is emerging as a promising prognostic factor in renal cell carcinoma (RCC). The most commonly used immunohistochemical (IHC) antibody has been criticized for its low specificity. In addition, blood levels of IMP3 have not yet been analyzed in RCC. Therefore, we compared the prognostic performance of two different IMP3 IHC antibodies and assessed the prognostic relevance of IMP3 plasma levels in RCC. IMP3 levels were assessed in an overall number of 425 RCC (344× clear cell [ccRCC], 63× papillary [pRCC], 18× chromophobe [chRCC]) patients in three partly overlapping cohorts. Plasma IMP3 concentrations were determined by ELISA in 98 RCC (79× ccRCC, 15× pRCC, 4× chRCC) patients and 20 controls. IMP3 mRNA expression levels were analyzed in 73 frozen tissue samples (55× ccRCC, 12× pRCC, 6× chRCC), while protein expressions were assessed in 366 FFPE samples (294× ccRCC, 56× pRCC, 16× chRCC) using the M3626 and N‐19 antibodies. IMP3 plasma and mRNA expression levels were significantly higher in patients compared to controls and in high‐grade compared to low‐grade tumors. In addition, IMP3 plasma and tissue protein levels (by M3626) were higher and IMP3 mRNA expression levels tended to be higher in patients with distant metastasis. Multivariate analyses in clear cell RCC revealed high IMP3 plasma concentration and mRNA expression as independent predictors of disease‐specific survival. IMP3 immunostainings by M3626 but not by N‐19 were independently associated with poor overall and disease‐specific survival. High plasma and tissue levels of IMP3 are independently associated with poor RCC prognosis. The applied antibody significantly impacts the prognostic performance of analysis. IMP3 analysis may improve risk‐stratification of RCC patients and therefore could help to optimize therapeutic and follow‐up decisions.

Szendroi RESULTS• MMP-7 levels did not differ significantly between patients with localized bladder cancer and controls ( P = 0.174). On the other hand, we detected a fourfold, significantly elevated MMP-7 concentration in urine samples of patients with bladder cancer with regional or distant metastasis ( P = 0.003).• Using a threshold value of 6.88 ng/ml, determined by receiver-operating characteristic curve analysis, a specificity of 82% and a sensitivity of 78% were observed.• Western blot analysis revealed that the 55-kDa tissue inhibitor of metalloproteinase 1 complexed MMP-7 is the dominant form of urinary matrilysin. CONCLUSIONS• MMP-7 is present in detectable amounts in the urine of patients with bladder cancer. Its concentrations are significantly elevated in patients with metastatic disease.• Determination of urinary matrilysin level could help to detect bladder cancer metastasis, and may therefore provide a more reliable prognosis and influence therapy decisions. KEYWORDSbladder cancer, MMP-7, matrilysin, urine, metastasis, prognosis What's known on the subject? and What does the study add? Recent data suggest that MMP-7 is critically involved in metastasis formation. In accordance, we formerly found significantly elevated MMP-7 tissue expression and serum concentration in samples of patients with metastatic bladder cancer and observed an independent correlation between MMP-7 levels and patients' prognosis. In the present study we demonstrated that high preoperative urinary MMP-7 concentrations are associated with metastatic bladder cancer. PATIENTS AND METHODS• The presence of MMP-7 in the urine of patients with bladder cancer was tested in 32 representative cases using immunoprecipitation followed by western blot analysis.• Urinary MMP-7 concentration levels were analyzed in 132 patients with bladder cancer and 96 controls using an enzyme-linked immunosorbent assay.