Diagnostic Accuracy of a MR Protocol Acquired with and without Endorectal Coil for Detection of Prostate Cancer: A Multicenter Study

Introduction The purpose of this study was to compare diagnostic accuracy of a prostate multiparametric magnetic resonance imaging (mpMRI) protocol for detection of prostate cancer between images acquired with and without en-dorectal coil (ERC). Materials This study was approved by the regional ethics committee. Between 2014 and 2015, 33 patients (median age 51.3 years; range 42.1-77.3 years) who underwent prostate-MRI at 3T scanners at 2 different institutions, acquired with (mpMRI) and without (mpMRI) ERC and who received radical prostatectomy, were included in this retrospective study. Two expert readers (R1, R2) attributed a PI-RADS version 2 score for the most suspect (i. e. index) lesion for mpMRI and mpMRI. Sensitivity and positive predictive value for detection of index lesions were assessed using 2 × 2 contingency tables. Differences between groups were tested using the McNemar test. Whole-mount histopathology served as reference standard. Results On a quadrant-basis cumulative sensitivity ranged between 0.61-0.67 and 0.76-0.88 for mpMRI and mpMRI protocols, respectively (p > 0.05). Cumulative positive predictive value ranged between 0.80-0.81 and 0.89-0.91 for mpMRI and mpMRI protocols, respectively. The differences were not statistically significant for R1 (p = 0.267) or R2 (p = 0.508). Conclusion Our results suggest that there may be no significant differences for detection of prostate cancer between images acquired with and without an ERC

Unreserved application of epigenetic methods to define differences of DNA methylation between urinary cellular and cell-free DNA

Urinary DNA is increasingly gaining importance in diagnosis of urological malignancies. Especially cell-free DNA originating from apoptotic and necrotic cells of the early tumor could become a key target for early stage tumor diagnosis. Aberrant DNA methylation forms tumor cell characteristic epigenetic profiles which are covalently established before any tumor related aberration at transcriptional or protein level has occurred. In addition, these epigenetic signatures are alterably adapted to and accompanying the individual stages of multistep, progressive tumorigenesis. Hence, they seem very promising for diagnosis as well as for monitoring the patient's follow-up care and even for decisions regarding personalized therapeutic options. The essential prerequisite at this approach will be a reliable methodological handling of the biological material of interest. In this study we present detailed analyses of LINE-1 DNA methylation profiles and demonstrate the sensitive detection of LINE-1 DNA methylation differences as well as between cancer patients and healthy individuals, between urinary cellular and cell-free DNA. In addition, we show methylome differences between both DNA fractions from a healthy individual and bladder cancer patients. In conclusion, we demonstrate here the unrestricted amenability of urinary cell-free DNA for both, a detailed characterization of a distinct DNA methylation alteration and its sensitive detection and a comprehensive global, array-based screening for DNA methylation differences

Expression of histone deacetylases 1,2 and 3 in urothelial bladder cancer

BACKGROUND: Histone deacetylases (HDACs) are known to be associated with an overexpression in different types of cancer such as colon and prostate cancer. In this study we aimed to evaluate the protein expression of class I HDACs in urothelial carcinoma of the bladder. METHODS: A tissue microarray containing 348 tissuesamples from 174 patients with a primary urothelial carcinoma of the bladder was immunohistochemically stained for (HDAC) 1, 2 and 3. Intensity of staining was evaluated and the association with clinico-pathological features and prognosis was assessed. RESULTS: High HDAC expression levels were found in 40 to 60% of all investigated urothelial carcinomas (HDAC-1: 40%, HDAC-2: 42%, HDAC-3: 59%).HDAC-1 and HDAC-2 were significantly associated with higher tumour grades.Although all three markers could not predict progression in univariate analyses, high HDAC-1 expression was associated with a trend toward poorer prognosis. Patients with high-grade tumours and high expression levels of HDAC-1 were more likely to progress compared to all other patients (p < 0.05). CONCLUSIONS: High-grade noninvasive papillary bladder tumours are associated with high expression levels of HDAC-1 and HDAC-2. High grade tumours in combination with high expression of HDAC-1 showed a worse prognosis than the other tumours. The high expression levels of HDACs observed particularly in high grade urothelial bladder cancer clearly warrant subsequent studies on the potential use of HDAC inhibitors as a novel therapeutic approach