BRCA testing in metastatic castration-resistant prostate cancer: successes and troubles in a real world setting. An Italian Multicentric study.

Objective: Prostate cancer (PCa) is the most common cause of cancer-related deaths in men worldwide. BRCA1/2 genes are reported altered in approximately 1% and 8% of PCa cases, respectively. To date, formalin-fixed paraffin-embedded (FFPE) tissues have a consolidate use in the clinical practice, but with a significant drawback related to DNA/RNA degradation during the pre-analytical process.

Effectiveness and Impact of Transcript Analysis in Clinical Genetics Daily Practice.

Broad-spectrum genetic tests often lead to the identification of variants of uncertain significance (VUS), a major issue in modern clinical genetics. A fair proportion of VUS may alter the splicing processes, but their interpretation is challenging. This study aimed at providing a classification approach for VUS potentially-affecting splicing by integrating transcript analysis from peripheral blood mRNA into routine diagnostics.

A Transcriptomic Analysis of Laryngeal Dysplasia.

This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery.

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype.

Importance: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation.

Objectives: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival.

Expression of immune-related genes and breast cancer recurrence in women with ductal carcinoma in situ.

Background And Aim: Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer with highly variable clinical behavior, but risk stratification is still challenging. We sought to identify immune-related gene expression signatures of pure DCIS associated with different risks of breast cancer recurrence.

Methods: A retrospective nested case-control study of 143 pure DCIS was performed including 70 women with subsequent ipsilateral breast event (IBE, in situ or invasive; cases) and 73 DCIS women with no IBE and matched for age, tumor size, treatment, hormone receptors/HER2 status, and follow-up time (controls).

Circulating tumour DNA testing in metastatic breast cancer: Integration with tissue testing.

Breast cancer biomarker profiling predominantly relies on tissue testing (surgical and/or biopsy samples). However, the field of liquid biopsy, particularly the analysis of circulating tumour DNA (ctDNA), has witnessed remarkable progress and continues to evolve rapidly. The incorporation of ctDNA-based testing into clinical practice is creating new opportunities for patients with metastatic breast cancer (MBC).

In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study.

Aims: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised.

The Genetic and Immunologic Landscape Underlying the Risk of Malignant Progression in Laryngeal Dysplasia.

(1) Background: The development of laryngeal cancer is a multistep process involving structural alterations of the epithelial mucosa, from dysplasia (LDy) to invasive carcinoma. In this study, we define new biomarkers, prognostic for malignant transformation, in patients affected by LDy. (2) Methods: We used targeted next-generation sequencing and immunohistochemical analysis to define the mutational and immunological landscape of 15 laryngeal dysplasia progressing to invasive cancer (progressing dysplasia), as well as 31 cases of laryngeal dysplasia that did not progress to carcinoma (non-progressing dysplasia).

Analytical Performance of Next-Generation Sequencing and RT-PCR on Formalin-Fixed Paraffin-Embedded Tumor Tissues for Testing in HR+/HER2- Breast Cancer.

Somatic mutations in are present in ~40% breast cancers (BC); their detection in hormone receptor (HR)+/HER2- tumors allows for selecting patients with advanced disease eligible for targeting with alpelisib. The choice of what type of testing approach to adopt and which tissue sample to analyze is a new task in breast pathology. In this methodological study, we sought to assess the performance of next-generation sequencing (NGS) and RT-PCR for testing on archival formalin-fixed paraffin-embedded (FFPE) primary tumors and corresponding metastases.

Phenotypic Spectrum and Molecular Findings in 17 ATR-X Syndrome Italian Patients: Some New Insights.

ATR-X syndrome is a rare X-linked congenital disorder caused by hypomorphic mutations in the gene. A typical phenotype is well defined, with cognitive impairment, characteristic facial dysmorphism, hypotonia, gastrointestinal, skeletal, urogenital, and hematological anomalies as characteristic features. With a few notable exceptions, general phenotypic differences related to specific ATRX protein domains are not well established and should not be used, at least at the present time, for prognostic purposes.

Integrative characterization of intraductal tubulopapillary neoplasm (ITPN) of the pancreas and associated invasive adenocarcinoma.

Pancreatic intraductal tubulopapillary neoplasm (ITPN) is a recently recognized intraductal neoplasm. This study aimed to clarify the clinicopathologic and molecular features of this entity, based on a multi-institutional cohort of 16 pancreatic ITPNs and associated adenocarcinomas. The genomic profiles were analyzed using histology-driven multi-regional sequencing to provide insight on tumor heterogeneity and evolution.

Integrative molecular analysis of combined small-cell lung carcinomas identifies major subtypes with different therapeutic opportunities.

Background: Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC.

Molecular characterization of extrahepatic cholangiocarcinoma: perihilar and distal tumors display divergent genomic and transcriptomic profiles.

Background: Extrahepatic cholangiocarcinoma (ECC) is classified into two subtypes based on anatomic origin: distal extrahepatic (DECC) and perihilar (PHCC) cholangiocarcinoma. This study aimed to shed light on its genomic and transcriptomic profiles.

Research Design And Methods: The genomic alterations of 99 ECC (47 PHCC and 52 DECC) were investigated by next-generation sequencing of 96 genes.

Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions.

Tumor mutational burden (TMB) is a numeric index that expresses the number of mutations per megabase (muts/Mb) harbored by tumor cells in a neoplasm. TMB can be determined using different approaches based on next-generation sequencing. In the case of high values, it indicates a potential response to immunotherapy.

Not Reinventing the Wheel: Adapting Treatment Foster Care Oregon to Public Mental Health.

Intervention adaptations expand the availability of evidence-based treatments across clinical settings and demographically different populations. These adaptations utilize systematic strategies to preserve core components of an intervention. Intervention adaptations made from one public system to another (e.

Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses.

Background: The breast cancer genome dynamically evolves during malignant progression and recurrence. We investigated the genomic profiles of primary early-stage breast cancers and matched relapses to elucidate the molecular underpinnings of the metastatic process, focusing on potentially actionable alterations in the recurrences.

Methods: A mono-institutional cohort of 128 patients with breast cancers (n = 68 luminal B HER2, n = 6 luminal B HER2+, n = 1 HER2+ non-luminal, n = 56 triple negative) and at least one recurrence in a timeframe of 17 years was evaluated.

Clinical characterization of status epilepticus in childhood: a retrospective study in 124 patients.

Purpose: The aim of this study is to describe demographic data, semiology and etiology in a pediatric population with status epilepticus (SE) and refractory SE (RSE).

Method: We retrospectively reviewed patients with the following inclusion criteria: i) age between two months and eighteen years; ii) SE diagnosis; iii) admission from January 2001 to December 2016; iv) available clinical data.

Results: We enrolled 124 patients.

SARS-CoV-2 detection in formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma.

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens.

Barriers to live donor kidney transplants in the pediatric population: A single-center experience.

A decrease in live donor pediatric kidney transplants has occurred in the United States. This study investigates barriers that may influence access to live donor kidney transplants in children. Retrospective chart review was conducted for 91 children (69% male, mean age 11.

Treatment Efficacy of Combined Sertraline and Guanfacine in Comorbid Obsessive-Compulsive Disorder and Attention Deficit/Hyperactivity Disorder: Two Case Studies.

Objective: Treatment of obsessive-compulsive disorder (OCD) is complicated by comorbid psychiatric disorders. Successful treatment of 2 pediatric patients with severe OCD and comorbid attention deficit/hyperactivity disorder (ADHD) is described.

Method: A report on 2 pediatric clinical cases (Ages 9 and 10) with comorbid OCD and ADHD was used to describe response to medication management through the serotonin transporter inhibitor, sertraline, and the noradrenergic α2A receptor agonist, guanfacine, along with cognitive behavioral therapy.

Is health-related quality of life associated with upper and lower airway inflammation in asthmatics?

Background: Allergic diseases impair health-related quality of life (HR-QoL). However, the relationship between airway inflammation and HR-QoL in patients with asthma and rhinitis has not been fully investigated. We explored whether the inflammation of upper and lower airways is associated with HR-QoL.

Alveolar nitric oxide and asthma control in mild untreated asthma.

Background: The role of the peripheral airways in asthma is increasingly being recognized as a potential target for the achievement of optimal control of the disease. We postulated that the inflammatory changes of the small airways are implicated in the lack of asthma control in mild asthma.

Objective: To test this hypothesis, we measured the alveolar fraction of exhaled NO (CalvNO) in patients with mild asthma with different levels of control of symptoms.

Prevalence of sexually transmitted infections and enteric protozoa among homosexual men in western Sicily (south Italy).

Introduction: In recent years an increase in the number of sexually transmitted infections (STIs) in men who have sex with men (MSM) has been reported in different industrialised countries. Because few epidemiological data on the STls/MSM population in Sicily are available, a survey was conducted to assess the prevalence of STls/enteric protozoa and risky sexual behaviours among MSM in western Sicily.

Methods: In 2010, 74 MSM with median age of 30 years old, were recruited via networks.

Medial temporal N-acetyl-aspartate in pediatric major depression.

The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD case-control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in the left MTC (27%) in MDD patients versus controls.