Hered Cancer Clin Pract
December 2024
Background: BRCA2 germline mutations are known to predispose carriers to various cancer types, including breast, ovarian, pancreatic and prostate cancer. An association with melanoma has also been reported. However, the full tumour spectrum associated with BRCA2 mutations, particularly in patients with other concurrent pathogenetic mutations, is unexplored.
View Article and Find Full Text PDFStringent control of T cell activity in the tumor microenvironment is essential for the generation of protective antitumor immunity. However, the identity, differentiation, and functions of the cells that create critical fibroblastic niches promoting tumor-infiltrating T cells remain elusive. Here, we show that CCL19-expressing fibroblastic reticular cells (FRCs) generate interconnected T cell environments (TEs) in human non-small cell lung cancer, including tertiary lymphoid structures and T cell tracks.
View Article and Find Full Text PDFBackground: The multi tyrosine kinase inhibitor regorafenib is active in metastatic colorectal cancer. Improvement in clinical outcome by adding regorafenib to long-course chemoradiotherapy (LcCRT) was investigated in molecularly undefined LARC.
Methods: Patients with T3-4 and/or N+ but M0 rectal cancer were included.
Somatic variant testing through next-generation sequencing (NGS) is well integrated into Swiss molecular pathology laboratories and has become a standard diagnostic method for numerous indications in cancer patient care. Currently, there is a wide variation in reporting practices within our country, and as patients move between different hospitals, it is increasingly necessary to standardize NGS reports to ease their reinterpretation. Additionally, as many different stakeholders-oncologists, hematologists, geneticists, pathologists, and patients-have access to the NGS report, it needs to contain comprehensive and detailed information in order to answer the questions of experts and avoid misinterpretation by non-experts.
View Article and Find Full Text PDFImportance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.
Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.
Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap) software. We aim to provide an update of the SEECS 8 years after its launch.
View Article and Find Full Text PDFThe majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters.
View Article and Find Full Text PDFAm J Respir Crit Care Med
October 2024
Immune checkpoint inhibitor (ICI)-related pneumonitis is a serious autoimmune event affecting as many as 20% of patients with non-small-cell lung cancer (NSCLC), yet the factors underpinning its development in some patients and not others are poorly understood. To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. The study cohort consisted of patients with NSCLC who provided blood samples before and during ICI treatment.
View Article and Find Full Text PDFDigital pathology (DP) is increasingly entering routine clinical pathology diagnostics. As digitization of the routine caseload advances, implementation of digital image analysis algorithms and artificial intelligence tools becomes not only attainable, but also desirable in daily sign out. The Swiss Digital Pathology Consortium (SDiPath) has initiated a Delphi process to generate best-practice recommendations for various phases of the process of digitization in pathology for the local Swiss environment, encompassing the following four topics: i) scanners, quality assurance, and validation of scans; ii) integration of scanners and systems into the pathology laboratory information system; iii) the digital workflow; and iv) digital image analysis (DIA)/artificial intelligence (AI).
View Article and Find Full Text PDFIn myelofibrosis, comorbidities (CMs) add prognostic information independently from the Dynamic International Prognostic Scoring System (DIPSS). The Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) offers a simple tool for CM assessment as it is calculable after having performed a careful history and physical examination, a small routine chemistry panel (including creatinine and liver enzymes) and a limited set of functional diagnostics. To assess the prognostic impact of the MDS-CI in addition to the DIPSS and the Mutation-Enhanced International Prognostic Scoring System (MIPSS)-70, we performed a retrospective chart review of 70 MF patients who had not received allogeneic stem cell transplantation (primary MF, n = 51; secondary MF, n = 19; median follow-up, 40 months) diagnosed at our institution between 2000 and 2020.
View Article and Find Full Text PDFBackground: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression.
View Article and Find Full Text PDFIn myelofibrosis, the C-reactive protein (CRP)/albumin ratio (CAR) and the Glasgow Prognostic Score (GPS) add prognostic information independently of the Dynamic International Prognostic Scoring System (DIPSS). Their prognostic impact, if molecular aberrations are considered, is currently unknown. We performed a retrospective chart review of 108 MF patients (prefibrotic MF n = 30; primary MF n = 56; secondary MF n = 22; median follow-up 42 months).
View Article and Find Full Text PDFAlthough ACE2 is the primary receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, a systematic assessment of host factors that regulate binding to SARS-CoV-2 spike protein has not been described. Here, we use whole-genome CRISPR activation to identify host factors controlling cellular interactions with SARS-CoV-2. Our top hit was a TLR-related cell surface receptor called leucine-rich repeat-containing protein 15 (LRRC15).
View Article and Find Full Text PDFBackground: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained.
Patients And Methods: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82).
Next-generation sequencing (NGS) of tumor cell-derived DNA/RNA to screen for targetable genomic alterations is now widely available and has become part of routine practice in oncology. NGS testing strategies depend on cancer type, disease stage and the impact of results on treatment selection. The European Society for Medical Oncology (ESMO) has recently published recommendations for the use of NGS in patients with advanced cancer.
View Article and Find Full Text PDFCancer treatment with immune checkpoint blockade (ICB) often induces immune-related adverse events (irAEs). We hypothesized that proteins coexpressed in tumors and normal cells could be antigenic targets in irAEs and herein described DITAS (discovery of tumor-associated self-antigens) for their identification. DITAS computed transcriptional similarity between lung tumors and healthy lung tissue based on single-sample gene set enrichment analysis.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity.
View Article and Find Full Text PDFObjectives: The natural history of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is still largely unknown. Since reports of second primary tumors (SPTs) in patients with HPV-related OPSCCs are increasing, a multifocal HPV infection, hinting a «virus-induced field effect», has been hypothesized. This study aimed to investigate the HPV-prevalence in normal appearing oropharyngeal tissue in patients with OPSCCs.
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