High success rate of first proficiency testing for RET fusions and RET mutations in lung and thyroid cancer samples by various methods.

This study describes the external quality assessment (EQA) scheme for molecular testing of RET alterations in non-small cell lung cancer (NSCLC), medullary thyroid carcinomas (MTC), and non-MTC. The lead panel institute and Quality Assurance Initiative in Pathology (Qualitätssicherungs-Initiative Pathologie [QuIP] GmbH) selected formalin-fixed paraffin-embedded (FFPE) tissue from MTC for RET mutation testing by next-generation sequencing (NGS) methods and FFPE tissue from NSCLC and non-MTC for RET gene fusion testing using either in situ hybridisation (ISH) or NGS methods, forming 3 sub-schemes of the EQA scheme. Tissue material underwent an internal validation phase followed by an external testing phase.

Evaluation of a miRNA-371a-3p Assay for Predicting Final Histopathology in Patients Undergoing Primary Nerve-sparing Retroperitoneal Lymphadenectomy for Stage IIA/B Seminoma or Nonseminoma.

Patients with marker-negative clinical stage IIA/B seminoma or nonseminoma represent a therapeutic challenge, as 20-30% might harbor nonmalignant histologies. MicroRNA 371a-3p (miR371) may represent a biomarker with diagnostic and predictive properties in testicular germ cell tumors (TGCTs). We evaluated the predictive accuracy of this biomarker in identifying the presence or absence of lymph node metastases (LNMs) in clinical stage IIA/B TGCT.

MET Fusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition.

Introduction: MET fusions have been described only rarely in NSCLC. Thus, data on patient characteristics and treatment response are limited. We here report histopathologic data, patient demographics, and treatment outcome including response to MET tyrosine kinase inhibitor (TKI) therapy in MET fusion-positive NSCLC.

Resistance to MET inhibition in MET-dependent NSCLC and therapeutic activity after switching from type I to type II MET inhibitors.

Objectives: Resistance to MET inhibition occurs inevitably in MET-dependent non-small cell lung cancer and the underlying mechanisms are insufficiently understood. We describe resistance mechanisms in patients with MET exon 14 skipping mutation (METΔ), MET amplification, and MET fusion and report treatment outcomes after switching therapy from type I to type II MET inhibitors.

Materials And Methods: Pre- and post-treatment biopsies were analysed by NGS (next generation sequencing), digital droplet PCR (polymerase chain reaction), and FISH (fluorescense in situ hybridization).

Efficacy and tolerability of regorafenib in pretreated patients with progressive CNS grade 3 or 4 gliomas.

Background: The phase 2 REGOMA trial suggested an encouraging overall survival benefit in glioblastoma patients at first relapse treated with the multikinase inhibitor regorafenib. Here, we evaluated the efficacy and side effects of regorafenib in a real-life setting.

Methods: From 2018 to 2021, 30 patients with progressive WHO CNS grade 3 or 4 gliomas treated with regorafenib (160 mg/day; first 3 weeks of each 4-week cycle) with individual dose adjustment depending on toxicity were retrospectively identified.

Quantum Cascade Laser-Based Infrared Imaging as a Label-Free and Automated Approach to Determine Mutations in Lung Adenocarcinoma.

Therapeutic decisions in lung cancer critically depend on the determination of histologic types and oncogene mutations. Therefore, tumor samples are subjected to standard histologic and immunohistochemical analyses and examined for relevant mutations using comprehensive molecular diagnostics. In this study, an alternative diagnostic approach for automatic and label-free detection of mutations in lung adenocarcinoma tissue using quantum cascade laser-based infrared imaging is presented.

TargetPlex FFPE-Direct DNA Library Preparation Kit for SiRe NGS panel: an international performance evaluation study.

Aim: Next generation sequencing (NGS) represents a key diagnostic tool to identify clinically relevant gene alterations for treatment-decision making in cancer care. However, the complex manual workflow required for NGS has limited its implementation in routine clinical practice. In this worldwide study, we validated the clinical performance of the TargetPlex FFPE-Direct DNA Library Preparation Kit for NGS analysis.

Detection of gene fusions using targeted next-generation sequencing: a comparative evaluation.

Background: Gene fusions represent promising targets for cancer therapy in lung cancer. Reliable detection of multiple gene fusions is therefore essential.

Methods: Five commercially available parallel sequencing assays were evaluated for their ability to detect gene fusions in eight cell lines and 18 FFPE tissue samples carrying a variety of known gene fusions.

Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing.

Outcome of immune checkpoint inhibition in cancer can be predicted by measuring PDL1 expression of tumor cells. Search for additional biomarkers led to tumor mutational burden (TMB) as surrogate marker for neoantigens presented. While TMB was previously determined via whole exome sequencing (WES), there have been approaches with comprehensive gene panels as well.

First report on two cases of pleomorphic dermal sarcoma successfully treated with immune checkpoint inhibitors.

Pleomorphic dermal sarcoma (PDS) is one of the most common sarcoma of the skin. Currently, limited treatment options exist for advanced stages of the disease. While immune checkpoint inhibitors (CPIs) have revolutionized cancer treatment options-their efficacy in PDS has not been explored yet.

Influence of Different Cell-Penetrating Peptides on the Antimicrobial Efficiency of PNAs in Streptococcus pyogenes.

Streptococcus pyogenes is an exclusively human pathogen causing a wide range of clinical manifestations from mild superficial infections to severe, life-threatening, invasive diseases. S. pyogenes is consistently susceptible toward penicillin, but therapeutic failure of penicillin treatment has been reported frequently.

Comparison of in Situ and Extraction-Based Methods for the Detection of ROS1 Rearrangements in Solid Tumors.

Clinical data confirmed that patients with ROS1 rearrangement are sensitive to specific inhibitors. Therefore, reliable detection of ROS1 rearrangements is essential. Several diagnostic techniques are currently available.

The Regulatory Small RNA MarS Supports Virulence of Streptococcus pyogenes.

Small regulatory RNAs (sRNAs) play a role in the control of bacterial virulence gene expression. In this study, we investigated an sRNA that was identified in Streptococcus pyogenes (group A Streptococcus, GAS) but is conserved throughout various streptococci. In a deletion strain, expression of mga, the gene encoding the multiple virulence gene regulator, was reduced.

Genome-wide analyses of small non-coding RNAs in streptococci.

Streptococci represent a diverse group of Gram-positive bacteria, which colonize a wide range of hosts among animals and humans. Streptococcal species occur as commensal as well as pathogenic organisms. Many of the pathogenic species can cause severe, invasive infections in their hosts leading to a high morbidity and mortality.

Inhibition of Growth and Gene Expression by PNA-peptide Conjugates in Streptococcus pyogenes.

While Streptococcus pyogenes is consistently susceptible toward penicillin, therapeutic failure of penicillin treatment has been reported repeatedly and a considerable number of patients exhibit allergic reactions to this substance. At the same time, streptococcal resistance to alternative antibiotics, e.g.