Background Significant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. This study was aimed at the evaluation of a set of established epigenetic biomarkers as a noninvasive tool for more accurate PCa categorization before radical prostatectomy (RP). Methods Quantitative methylation-specific PCR was applied for the methylation analysis of RARB , RASSF1 , and GSTP1 in 514 preoperatively collected voided or catheterized urine samples from the single-centre cohort of 1056 treatment-naïve PCa patients who underwent RP. The rates of biopsy upgrading and upstaging were analysed in the whole cohort. Results Pathological examination of RP specimens revealed Gleason score upgrading in 27.2% and upstaging in 20.3% of the patients with a total misclassification rate of 39.0%. DNA methylation changes in at least one gene were detected in more than 80% of urine samples. Combination of the PSA test with the three-gene methylation analysis in urine was a significant predictor of pathological upstaging and upgrading ( P < 0.050), however, with limited increase in overall accuracy. The PSA test or each gene alone was not informative enough. Conclusions The urinary DNA methylation assay in combination with serum PSA may predict tumour stage or grade migration post-RP aiding in improved individual risk assessment and appropriate treatment selection. Clinical utility of these biomarkers should be proven in larger multi-centre studies. Electronic supplementary material The online version of this article (10.1186/s13148-019-0716-z) contains supplementary material, which is available to authorized users.

No abstract

The molecular diversity of prostate cancer (PCa) has been demonstrated by recent genome-wide studies, proposing a significant number of different molecular markers. However, only a few of them have been transferred into clinical practice so far. The present study aimed to identify and validate novel DNA methylation biomarkers for PCa diagnosis and prognosis. Microarray-based methylome data of well-characterized cancerous and noncancerous prostate tissue (NPT) pairs was used for the initial screening. Ten protein-coding genes were selected for validation in a set of 151 PCa, 51 NPT, as well as 17 benign prostatic hyperplasia samples. The Prostate Cancer Dataset (PRAD) of The Cancer Genome Atlas (TCGA) was utilized for independent validation of our findings. Methylation frequencies of ADAMTS12, CCDC181, FILIP1L, NAALAD2, PRKCB, and ZMIZ1 were up to 91% in our study. PCa specific methylation of ADAMTS12, CCDC181, NAALAD2, and PRKCB was demonstrated by qualitative and quantitative means (all p < 0.05). In agreement with PRAD, promoter methylation of these four genes was associated with the transcript down-regulation in the Lithuanian cohort (all p < 0.05). Methylation of ADAMTS12, NAALAD2, and PRKCB was independently predictive for biochemical disease recurrence, while NAALAD2 and PRKCB increased the prognostic power of multivariate models (all p < 0.01). The present study identified methylation of ADAMTS12, NAALAD2, and PRKCB as novel diagnostic and prognostic PCa biomarkers that might guide treatment decisions in clinical practice.

The primary objective of this study was to demonstrate the high accuracy of multiparametric magnetic resonance imaging and ultrasound fusion (mpMRI/US)-guided targeted prostate biopsy for the detection of clinically significant prostate cancer (PCa) and to show that adapted systematic biopsy (AdSB) does not provide additional benefit in detecting clinically significant prostate cancer (PCa). In total, 283 patients have been included in the study. All patients underwent the mpMRI/US biopsies, which have been performed with the “BioJet” fusion system (D&K Technologies, Barum, Germany) using the transperineal approach by a single interventional radiologist. Lesion-targeted and systematic biopsies have been done when 2–4 cores have been taken from each PI-RADS 3–5 lesion, followed by AdSB. This study demonstrated that targeted prostate biopsy is sufficient for safe and sensitive identification of clinically significant PCa in primary biopsy-naïve cases without the need to perform adapted systematic biopsy.

Aim: We investigated whether a difference exists between TSHR, PTEN and RASSF1A methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in TSHR, PTEN and RASSF1A genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of TSHR was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (p = 0.040). TSHR methylation levels in the PTC group plasma samples were significantly higher compared to HC (p = 0.022). After surgery, PTC plasma samples showed lower TSHR and PTEN methylation levels compared to the levels before surgery (p = 0.003, p = 0.031, respectively). The TSHR methylation level was significantly higher in PTC with larger tumor size (>2 cm) (p < 0.001), and lymph node metastases (p = 0.01), lymphovascular invasion (p = 0.02) and multifocality (p = 0.013) 0ROC analysis revealed that the TSHR methylation level provides high accuracy in distinguishing PTC from HC (p = 0.022, AUC of 0.616). Conclusion: TSHR methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means.

No abstract

No abstract

patients (6.84%), 8 men and 5 women in the age range 27 -81 years. Among the clinically most relevant fusions were identified ALK fusions (3 pts), ROS fusions (3 pts), and RET fusion (1 pt). 9 patients with detected EGFR mutations received targeted treatment. In additional 5 patients the targeted therapeutics are planned. Targeted treatment was administrated to 5 patients with detected gene fusions, mainly ALK and ROS1, in one patient the targeted therapy is planned. Conclusions:The introduction of sequencing techniques brings the relevant information about actionable molecular alterations into the multimodal management of lung cancer patients. As we showed in our study, the use of targeted NGS panel is a reliable approach for NSCLC molecular profiling and can be applied in personalized treatment decision making in routine clinical care of lung cancer patients.Legal entity responsible for the study: The authors.