Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

In the current study, expression levels of let-7c, miR-30c, miR-141, and miR-375 in plasma from 59 prostate cancer (PC) patients with different clinicopathological characteristics and two groups of controls: 16 benign prostatic hyperplasia (BPH) samples and 11 young asymptomatic men (YAM) were analyzed to evaluate their diagnostic and prognostic value in comparison to prostate-specific antigen (PSA). miR-375 was significantly downregulated in 83.5% of patients compared to BPH controls and showed stronger diagnostic accuracy (area under the curve [AUC]=0.809, 95% CI: 0.697-0.922, p=0.00016) compared with PSA (AUC=0.710, 95% CI: 0.559-0.861, p=0.013). Expression levels of let-7c showed potential to distinguish PC patients from BPH controls with AUC=0.757, but the result did not reach significance. Better discriminating performance was observed when combinations of studied biomarkers were used. Sensitivity of 86.8% and specificity of 81.8% were reached when all biomarkers were combined (AUC=0.877) and YAM were used as calibrators. None of the studied microRNAs (miRNAs) showed correlation with clinicopathological characteristics. PSA levels were significantly correlated with the Gleason score, tumor stage, and lymph node metastasis with Spearman correlation coefficients: 0.612, 0.576, and 0.458. In conclusion, the combination of the studied circulating plasma miRNAs and serum PSA has the potential to be used as a noninvasive diagnostic biomarker for PC screening outperforming the PSA testing alone.

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

Pilomatrix carcinoma is a rare skin tumor with an origin from hair matrix cells. The tumor is locally aggressive with a great tendency for recurrence, but the metastatic potential is limited. A pilomatrix carcinoma in 76-year-old female with lymph node metastases is presented. In addition to classical histopathological criteria and DNA ploidy analysis, a broad panel of antibodies was used for evaluation of the metastatic potential. Both primary tumor and lymph node metastasis revealed extremely high proliferation and apoptotic rates. High constant expressions of CD44v6 and P-cadherin were also observed. In the metastasis, significant reduction of E-cadherin and beta-catenin was detected. The best approach for assessment of metastatic potential of pilomatrix carcinoma seems to be the complex evaluation of routine histological criteria like vessel invasion, mitotic index, apoptotic count, and new molecular markers of cell death and adhesion.

Our data indicated that p53, BRCA1, ATM, PIK3CA, and HER2 alterations specifically correlate with clinicopathological characteristics of Bulgarian patients with breast cancer. Of these genes, only mutated p53 showed significant, though not independent, negative effect on overall survival.