Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal.

Background: The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case-control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer.

Methods: A research questionnaire was administered every two years to collect information on exposures and disease.

Common Variant in ALDH2 Modifies the Risk of Breast Cancer Among Carriers of the p.K3326* Variant in BRCA2.

Purpose: The p.K3326* variant is considered a low-penetrance variant for breast cancer. Aldehydes that accumulate in cells under insufficient aldehyde oxidation were most recently shown to trigger carcinogenesis by promoting depletion of BRCA2 protein.

Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield: Results from a nationwide prospective cohort.

Approximately 5% of patients with colorectal cancer (CRC) have a Mendelian predisposition for the disease. Identification of the disease-causing genetic variant enables carrier testing and tailored cancer prevention within affected families. To determine the panorama and genetic variation of Mendelian CRC syndromes among referrals at the cancer genetics clinics in Sweden, 850 patients clinically selected for CRC genetic investigation were included in a prospective study that tested for all major hereditary polyposis and nonpolyposis CRC conditions.

The Small Round Cell Sarcomas Complexities and Desmoplastic Presentation.

Background: Small round cell sarcomas (SRCSs) account for most solid malignancies in the pediatric age group and are a part of group of malignant tumors characterized by heterogenous clinical presentation and overlapping microscopic features of small, round, primitive cells. In addition to the recently established certain genetically defined subset of undifferentiated round cell sarcomas of soft tissue and bone, this group of sarcomas include desmoplastic small round cell tumor, poorly differentiated synovial sarcoma, alveolar rhabdomyosarcoma, mesenchymal chondrosarcoma, and small cell osteosarcoma. Although, those entities share clinical and cytomorphologic features and cannot be unequivocally classified based on clinical presentation and morphology alone.

A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias.

Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed.

The diagnostic utility of DNA copy number analysis of core needle biopsies from soft tissue and bone tumors.

Morphologic and immunohistochemical analysis of preoperative core needle biopsies (CNB) is important in the management of patients with soft tissue and bone tumors (STBTs). Most SBTB subtypes have more or less extensive DNA copy number aberrations (CNA), potentially providing useful diagnostic information. To evaluate the technical feasibility of single nucleotide polymorphism (SNP) array analysis and the diagnostic usefulness of the copy number profiles, we studied CNBs from 171 patients with suspected STBTs.

Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor.

Background: There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs.

Transcriptional profiling demonstrates altered characteristics of CD8 cytotoxic T-cells and regulatory T-cells in TP53-mutated acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) patients have limited effect from T-cell-based therapies, such as PD-1 and CTLA-4 blockade. However, recent data indicate that AML patients with TP53 mutation have higher immune infiltration and other immunomodulatory therapies could thus potentially be effective. Here, we performed the transcriptional analysis of distinct T-cell subpopulations from TP53-mutated AML to identify gene expression signatures suggestive of altered functional properties.

Parkinson's disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein-induced changes in maturation and immune reactive properties.

SignificanceOur results demonstrate the existence of early cellular pathways and network alterations in oligodendrocytes in the alpha-synucleinopathies Parkinson's disease and multiple system atrophy. They further reveal the involvement of an immune component triggered by alpha-synuclein protein, as well as a connection between (epi)genetic changes and immune reactivity in multiple system atrophy. The knowledge generated in this study could be used to devise novel therapeutic approaches to treat synucleinopathies.

The impact of oophorectomy on survival from breast cancer in patients with CHEK2 mutations.

Background: To estimate the impact of oophorectomy and other treatments on the survival of breast cancer patients with a CHEK2 mutation.

Methods: Women with Stage I-III breast cancer who were treated at 17 hospitals in Poland were tested for four founder mutations in the CHEK2 gene. 974 women (10%) were positive for a CHEK2 mutation.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

Objective: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress.

Design: Retrospective, observational.

Setting: Nationwide.

The Prognostic Role of Intratumoral Stromal Content in Lobular Breast Cancer.

Previous studies have shown that high intratumoral stromal content is associated with a worse prognosis in breast cancer, especially in the triple-negative subtype. However, contradictory results have been reported for estrogen-receptor-positive (ER+) breast cancer, indicating that the prognostic role of intratumoral stromal content may be subtype-dependent. In this study, we investigated the importance of intratumoral stromal content for breast cancer-specific mortality (BCM) in a well-defined subgroup ( = 182) of ER+/human-epidermal growth-factor-receptor-2 negative (HER2-) invasive lobular breast cancer (ILC).

Diagnostic Efficacy of Rectal Suction Biopsy with Regard to Weight in Children Investigated for Hirschsprung's Disease.

Background/aim: Diagnostic efficacy, defined as the percentage of rectal suction biopsy (RSB) specimens sufficient enough to determine the absence of ganglia cells in Hirschsprung's disease (HD) diagnosis, has been reported to be low, requiring repeated biopsies. The aim was to explore whether RSB diagnostic efficacy was influenced by the child's weight and to ascertain whether RSB efficacy differed between aganglionic and ganglionic tissue.

Materials And Methods: Efficacy analyses were conducted in a national HD-center's register on children 0-15 kg, examined between 2011-2019.

Unsupervised cluster analysis and subset characterization of abnormal erythropoiesis using the bioinformatic Flow-Self Organizing Maps algorithm.

Background: The Flow-Self Organizing Maps (FlowSOM) artificial intelligence (AI) program, available within the Bioconductor open-source R-project, allows for an unsupervised visualization and interpretation of multiparameter flow cytometry (MFC) data.

Methods: Applied to a reference merged file from 11 normal bone marrows (BM) analyzed with an MFC panel targeting erythropoiesis, FlowSOM allowed to identify six subpopulations of erythropoietic precursors (EPs). In order to find out how this program would help in the characterization of abnormalities in erythropoiesis, MFC data from list-mode files of 16 patients (5 with non-clonal anemia and 11 with myelodysplastic syndrome [MDS] at diagnosis) were analyzed.

Co-testing in cervical screening among 40- to 42-year-old women is unreasonable.

Introduction: The screening program for cervical cancer in Sweden recommends the use of primary human papillomavirus (HPV) screening for women aged ≥30 to 65 years. Co-testing with both HPV analysis and cytology is recommended at the first screening after the age of 40 years. To fulfil co-testing, all screened women aged 40-42 years within the region of Skåne were co-tested.

Encrustation of the ureteral double-J Stents made of styrene/ethylene/butylene and polyurethane before and after implantation.

Purpose: The aim of this study was to determine the affinity to crystal, calculi and biofilm deposition on ureteral double-J stents (DJ stents) after ureterorenoscopic-lithotripsy procedure (URS-L). The analysis was performed in two aspects: to determine which material used for fabricating ureteral stents promotes encrustation and which part of the DJ stents is the most vulnerable for blockage.

Methods: One hundred and twenty patients with an indwelling DJ stent duration between 7 and 78 days were included in this study.

Overlapping morphological, immunohistochemical and genetic features of superficial CD34-positive fibroblastic tumor and PRDM10-rearranged soft tissue tumor.

Superficial CD34-positive fibroblastic tumor (SCD34FT) is a recently recognized soft tissue tumor that is considered to be of borderline malignancy. The pathogenesis of this tumor remains incompletely understood, but it has been suggested that SCD34FT overlaps with tumors showing fusions involving the PRDM10 gene. Previous analyses of PRDM10-rearranged tumors have demonstrated that they have a distinct gene expression profile, resulting in high expression of CADM3 (also known as SynCam3), which can be detected immunohistochemically.

T cell receptor (TCR) signaling in health and disease.

Interaction of the T cell receptor (TCR) with an MHC-antigenic peptide complex results in changes at the molecular and cellular levels in T cells. The outside environmental cues are translated into various signal transduction pathways within the cell, which mediate the activation of various genes with the help of specific transcription factors. These signaling networks propagate with the help of various effector enzymes, such as kinases, phosphatases, and phospholipases.

Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care.

Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis.

Blood Copper Levels and the Occurrence of Colorectal Cancer in Poland.

There is a need for sensitive and specific biomarkers for the early detection of colorectal cancer. In this retrospective study, we assessed whether a high blood copper level was associated with the presence of colorectal cancer. The blood copper level was measured among 187 colorectal cancer patients and 187 matched controls.

Do BARD1 Mutations Confer an Elevated Risk of Prostate Cancer?

The current cancer testing gene panels tend to be comprehensive rather than site-specific. is one of the genes commonly included in the multi-cancer testing panels. Mutations in confer an increase in the risk for breast cancer, but it is not studied whether or not they predispose to prostate cancer.

Transcriptomics paving the way for improved diagnostics and precision medicine of acute leukemia.

Transcriptional profiling of acute leukemia, specifically by RNA-sequencing or whole transcriptome sequencing (WTS), has provided fundamental insights into its underlying disease biology and allows unbiased detection of oncogenic gene fusions, as well as of gene expression signatures that can be used for improved disease classification. While used as a research tool for many years, RNA-sequencing is becoming increasingly used in clinical diagnostics. Here, we highlight key transcriptomic studies of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) that have improved our biological understanding of these heterogeneous malignant disorders and have paved the way for translation into clinical diagnostics.