Somatic and Germline Variants Affect Prognosis and Susceptibility in Prostate Cancer.

BACKGROUND/AIM: Prostate cancer (PCa) is one of the most common tumors in men accounting for the 7.3% of all cancer-associated diseases in 2020. In advanced stage, this pathology is a lethal disease and is the fifth cause of cancer death in men worldwide. The diagnosis of PCa is performed by prostate-specific antigen (PSA) detection combined with direct rectal examination (DRE). However, high PSA levels can be detected in non-malignant conditions leading to overtreatment of non-oncological patients. Moreover, PSA levels are not associated with disease progression; therefore, the research of novel biomarkers could improve diagnosis and prognosis of this tumor. In this regard, genetic polymorphisms may affect PCa outcome as well as to be associated with cancer familiarity. In fact, germline variations detected in different genes including BRCA1, BRCA2, ATM and HOXB13 seem to be associated with PCa susceptibility and progression. MATERIALS AND METHODS: Somatic and germline polymorphisms were detected by next generation sequencing (NGS) in 48 PCa subjects and paired controls. Gene variants were matched with patient outcome and cancer familiarity to identify mutations linked to prognosis and tumor predisposition. RESULTS: NGS sequencing has allowed to identify different genetic polymorphisms that could be linked to cancer outcome and predisposition. In particular, somatic and germline mutations found in ATM, FOXA1 and SPOP genes correlate with poor prognosis and/or high Gleason score. Moreover, germline variants lying mainly in ATM, but also in ZFHX3, SPOP, CHD1, CDK12 and APC seem to be associated with hereditary-predisposing cancer syndrome. CONCLUSION: Variants correlating with poor prognosis and cancer susceptibility could be usable as possible tumor biomarkers in prostate cancer.

Detection of disease-causing mutations in prostate cancer by NGS sequencing.

Gene mutations may affect the fate of many tumors including prostate cancer (PCa); therefore, the research of specific mutations associated with tumor outcomes might help the urologist to identify the best therapy for PCa patients such as surgical resection, adjuvant therapy or active surveillance. Genomic DNA (gDNA) was extracted from 48 paraffin-embedded PCa samples and normal paired tissues. Next, gDNA was amplified and analyzed by next-generation sequencing (NGS) using a specific gene panel for PCa. Raw data were refined to exclude false-positive mutations; thus, variants with coverage and frequency lower than 100× and 5%, respectively were removed. Mutation significance was processed by Genomic Evolutionary Rate Profiling, ClinVar, and Varsome tools. Most of 3000 mutations (80%) were single nucleotide variants and the remaining 20% indels. After raw data elaboration, 312 variants were selected. Most mutated genes were KMT2D (26.45%), FOXA1 (16.13%), ATM (15.81%), ZFHX3 (9.35%), TP53 (8.06%), and APC (5.48%). Hot spot mutations in FOXA1, ATM, ZFHX3, SPOP, and MED12 were also found. Truncating mutations of ATM, lesions lying in hot spot regions of SPOP and FOXA1 as well as mutations of TP53 correlated with poor prognosis. Importantly, we have also found some germline mutations associated with hereditary cancer-predisposing syndrome. gDNA sequencing of 48 cancer tissues by NGS allowed to detect new tumor variants as well as confirmed lesions in genes linked to prostate cancer. Overall, somatic and germline mutations linked to good/poor prognosis could represent new prognostic tools to improve the management of PCa patients.

Tubeless procedure reduces hospitalization and pain after percutaneous nephrolithotomy: results of a multivariable analysis.

The objective of the study was to assess the efficacy and safety of tubeless percutaneous nephrolithotomy (t-PCNL) in comparison with standard PCNL (s-PCNL). We retrospectively evaluated 317 consecutive PCNL and compared perioperative results, time of hospitalization and analgesic requirement of t-PCNL (114; 36.0 %) to s-PCNL (203; 64.0 %). The decision to perform a tubeless PCNL was made at the end of the procedures depending on the surgeon's preference and according to the following inclusion criteria: (a) no serious bleeding or perforation in the collecting system during the procedure; (b) patients with no more than one access; and (c) residual stone burden needing a second-stage nephroscopy. Staghorn stones and anatomic anomalies were not considered as exclusion criteria for t-PCNL. Univariate analyses were conducted with one-way ANOVA, Fisher's exact test, Pearson's Chi-square and linear-by-linear association test as appropriate. Stepwise multivariable regression analyses were used to assess the independent correlation between demographics and clinical variables and the clinical outcomes. There were no significant differences between the two groups in terms of stone-free rate, hemoglobin decrease, blood transfusion and complication rate. Mean hospital stay was significantly shorter in the t-PCNL group (3.3 vs. 4.6 days; P < 0.001). Tubeless PCNL was associated with less analgesia requirement (68.4 vs. 86.7 %; P < 0.001) and with lower analgesic dose requirement (1.6 vs. 2.1 mean doses; P = 0.010). Multivariable analyses showed that t-PCNL (P < 0.001), postoperative fever (P < 0.001), transfusions (P < 0.001), operative time (P = 0.002), postoperative hydronephrosis (P = 0.005) and residual fragment dimension (P = 0.024) were independently correlated with duration of hospitalization, while analgesic dose requirement was independently influenced by hemoglobin decrease (P < 0.001), t-PCNL (P = 0.005) and stone number (P = 0.044). Our study confirmed that t-PCNL has similar outcomes to s-PCNL in terms of stone-free rate without increasing complications in selected cases. t-PCNL is a factor independently associated with shorter hospitalization and lower analgesic requirement.

Testicular sclerosing Sertoli cell tumor: an additional case and review of the literature.

Sertoli cell tumours are very rare testicular tumours accounting for 0.4-1.5% of all testicular neoplasms. In the current report, we present a case of sclerosing Sertoli cell tumour. The histology and clinical features were compared to those of other Sertoli cell tumour subtypes in order to assess if the different subtypes really represent distinct clinical and prognostic entities. The current literature was also reviewed. Only 20 cases of sclerosing Sertoli cell tumours have been encountered. Our case, a 38-year-old man represents the 21st case. Distinction among Sertoli cell tumours is important not only histologically; sclerosing Sertoli cell tumours have a distinct clinical behaviour and prognosis, different from those of classic and large-cell calcifying Sertoli cell tumours. Pathologists and urologists should know and understand all the types of Sertoli cell tumours in order to be able to choose the correct therapeutical approach when they encounter these tumours.