SLC1A5 is a key regulator of glutamine metabolism and a prognostic marker for aggressive luminal breast cancer.

Cancer cells exhibit altered metabolism, often relying on glutamine (Gln) for growth. Breast cancer (BC) is a heterogeneous disease with varying clinical outcomes. We investigated the role of the amino acid transporter SLC1A5 (ASCT2) and its association with BC subtypes and patient outcomes.

Prediction of response to anti-HER2 therapy using a multigene assay.

HER2-positive breast cancer (BC), which constitutes 13-15% of cases, shows variable response to anti-HER2 therapies. HER2-positivity, defined as protein overexpression (immunohistochemistry (IHC) score 3+) or equivocal expression (IHC 2+) with evidence of HER2 gene amplification, determines the eligibility to anti-HER2 therapy. MammaTyper® assay (Cerca Biotech GmbH) is a RT-qPCR BC subtyping platform based on the mRNA expression of ERBB2, ESR1, PGR, and MKI67.

Molecular and genetic analysis of methicillin-resistant Staphylococcus aureus (MRSA) in a tertiary care hospital in Saudi Arabia.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to pose significant challenges in healthcare settings due to its multi-drug resistance (MDR) and virulence. This retrospective study examines the molecular and resistance profiles of MRSA isolates from a tertiary care hospital in Saudi Arabia, providing valuable insights into regional epidemiology. A total of 190 MRSA strains were analysed to assess antimicrobial susceptibility, genetic diversity, and virulence factors.

Diagnostic interobserver variability of atypia assessment in columnar cell lesions among a group of expert breast pathologists in the United Kingdom and the Republic of Ireland, on behalf of the UK national coordinating committee for breast pathology.

Aims: Atypical ductal hyperplasia and flat epithelial atypia (FEA) have defined diagnostic criteria, yet there is variation in the interpretation of these criteria, particularly when the atypia is present in a background of columnar cell lesions (CCLs). This study focuses upon cases which are especially challenging or difficult to classify reproducibly according to existing criteria.

Methods And Results: Thirteen breast pathology experts were asked to classify 10 challenging cases with CLLs as atypical or non-atypical.

Identifying multidrug-resistant organisms in diabetic foot ulcers: a study of risk factors and antimicrobial resistance genes.

This study aims to evaluate the antibiotic susceptibility profiles of bacterial isolates from DFU patients, identify the prevalence of MDROs, and identify specific risk factors contributing to these infections to inform effective antibiotic treatment strategies. This prospective cohort study included 187 DFU patients from March 2023 to February 2024 at King Khalid Hospital, Saudi Arabia. The exclusion criteria were nondiabetic ulcers, specific infections, tumours, or recent antibiotic use.

Nuclear morphological characterisation of lobular carcinoma variants: a morphometric study.

Background And Aims: Lobular carcinoma (LC) of the breast exhibits diverse morphology and clinical behaviour. The pleomorphic variant (pLC) displays distinct cytonuclear features and aggressiveness compared to the classic variant (cLC). However, diagnosing pLC remains subjective.

Deciphering the Role of ASPM in Breast Cancer: A Comprehensive Multicohort Study.

Background: Assembly factor for spindle microtubules (ASPM) has gained significant attention in cancer research due to its association with tumor growth and progression. Through the analysis of large-scale genomic datasets, ASPM has been identified as the top upregulated gene in breast cancer (BC), characterized by high proliferation. This multicohort study aimed to investigate the clinicopathological and prognostic significance of ASPM mRNA and protein expression in BC.

Cell cycle traverse rate predicts long-term outcomes in a multi-institutional cohort of patients with triple-negative breast cancer.

Background: Ki67 index (KI) and mitotic index (MI) are proliferation markers with established prognostic value in breast carcinomas. While KI is evaluated immunohistochemically and reported as a percentage, MI is determined visually and reflects total mitotic cells in 10 high-power fields. Our objective was to integrate KI and MI into a novel metric; the cell cycle traverse rate (CCTR).

Hydroxyacid Oxidase 1, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Luminal Breast Cancer.

Breast cancer (BC), which remains the most prevalent malignancy among women, is characterised by significant heterogeneity across its molecular subtypes. Oestrogen receptor-positive (ER+) (luminal) BC represents approximately 75% of cases, and despite advancements in treatment there remains around a 40% recurrence rate. Cellular uptake of glutamine is conducted by solute carriers (SLCs), which are significantly associated with outcome in luminal BC.

Geometric characteristics of stromal collagen fibres in breast cancer using differential interference contrast microscopy.

Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue.

Induction of the TEAD Coactivator VGLL1 by Estrogen Receptor-Targeted Therapy Drives Resistance in Breast Cancer.

Resistance to endocrine therapies (ET) is common in estrogen receptor (ER)-positive breast cancer, and most relapsed patients die with ET-resistant disease. Although genetic mutations provide explanations for some relapses, mechanisms of resistance remain undefined in many cases. Drug-induced epigenetic reprogramming has been shown to provide possible routes to resistance.

Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with Clinical Outcome.

Protein tyrosine kinase 7 (PTK7), originally known as colon carcinoma kinase (CCK4), is an evolutionary conserved, catalytically defective transmembrane receptor involved in Wnt signalling. PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer. PTK7 protein expression was evaluated in 1136 early-stage invasive breast tumours by immunohistochemistry.

HER2-positive grade 1 invasive carcinomas of the breast.

Aims: The American Society of Clinical Oncology and College of American Pathologists HER2-guidelines recommend repeat testing for most grade 1 mammary carcinomas that are HER2-positive in the core biopsy. This study aimed to assess the value of repeat HER2-testing and the histological features of HER2-positive grade 1 carcinomas.

Methods And Results: A case-series of HER2-results of grade 1 carcinomas was conducted of patients with no pre-operative systemic treatment over a 5-year period.

Revisiting surgical margins for invasive breast cancer patients treated with breast conservation therapy - Evidence for adopting a 1 mm negative width.

Clinical trials have demonstrated conclusively the non-inferiority of breast-conserving surgery followed by breast radiation therapy (BCT) compared with mastectomy for the treatment of early-stage invasive breast cancer (BC). The definition of the required surgical margin to ensure adequate removal of the cancer by BCT to obtain an acceptable low local recurrence (LR) rate remains controversial. Meta-analyses published by Houssami et al.

The Conflicting Prognostic Role of the Stroma-Tumor Ratio in Breast Cancer Molecular Subtypes.

The tumor microenvironment plays a key role in tumor progression. The proportion of the stroma-to-tumor cells (stroma-tumor ratio [STR]) has a variable prognostic significance in breast cancer (BC) molecular classes. In this study, we evaluated the mechanisms of stroma formation and composition in different molecular subtypes, which could explain the different prognostic values.

Controversies regarding encapsulated papillary carcinoma of the breast: an approach to evaluation and categorisation.

Malignant papillary lesions, and in particular, encapsulated papillary carcinoma (EPC) of the breast, continue to present diagnostic challenges for the practising pathologist. In addition to the relative rarity of these lesions, the lack of evidence-based diagnostic criteria, differences in the biological characteristics, and the clinical behaviour of in situ and invasive forms, variable use of immunohistochemical markers, and overlap with other tumour types including high-grade circumscribed forms of invasive breast carcinomas has resulted in diagnostic discordance with potentially significant clinical and management implications. Pathologists should be familiar with the range of morphology observed in malignant papillary tumours, EPC, and EPC-like tumours and the existence of tumours with overlapping features.

Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer.

Introduction: Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC.

What factors influence cellular pathologists' confidence in case reporting?

Histopathology is a challenging interpretive discipline, and the level of confidence a pathologist has in their diagnosis is known to vary, which is conveyed descriptively in pathology reports. There has been little study to accurately quantify pathologists' diagnostic confidence or the factors that influence it. In this study involving sixteen pathologists from six NHS trusts, we assessed diagnostic confidence across multiple variables and four specialties.

The role of the ALKBH5 RNA demethylase in invasive breast cancer.

Background: N6-methyladenosine (mA) is the most common internal RNA modification and is involved in regulation of RNA and protein expression. AlkB family member 5 (ALKBH5) is a mA demethylase. Given the important role of mA in biological mechanisms, mA and its regulators, have been implicated in many disease processes, including cancer.

A novel Na1.5-dependent feedback mechanism driving glycolytic acidification in breast cancer metastasis.

Solid tumours have abnormally high intracellular [Na]. The activity of various Na channels may underlie this Na accumulation. Voltage-gated Na channels (VGSCs) have been shown to be functionally active in cancer cell lines, where they promote invasion.