Roche Digital Pathology Dx whole slide imaging system is comparable to traditional microscopy for primary diagnosis in surgical pathology.

Objective: We evaluated the clinical performance of Roche Digital Pathology Dx, a whole slide imaging (WSI) system, in 2 studies according to US Food and Drug Administration (FDA) and Digital Pathology Association criteria.

Methods: Precision was measured by pathologists identifying 23 histopathology features; accuracy was assessed by comparing diagnoses from 2047 clinical cases with those from manual microscopy, with exploratory analyses including subgroup-specific diagnostic discrepancy rates.

Results: Both studies met all predetermined primary endpoints.

Nonlinear progression during the occult transition establishes cancer lethality.

Cancer screening relies upon a linear model of neoplastic growth and progression. Yet, historical observations suggest that malignant progression is uncoupled from growth, which may explain the paradoxical increase in early-stage breast cancer detection without a dramatic reduction in metastasis. Here, we lineage trace millions of transformed cells and thousands of tumors using a cancer rainbow mouse model of HER2 (also known as ERBB2)-positive breast cancer.

Adaptive selection of p53 mutation metaplastic phenotypes in estrogen-independent progression of ER+ tumors: A mechanism for acquired resistance to hormonal therapy.

Estrogen receptor positive (ER ) subtypes of mammary adenocarcinoma comprise 79% of all breast cancer diagnosis and 67% of all breast cancer mortality. The paucity of models of ER mammary cancer that mimic human disease and response to treatment has limited critical preclinical study of mechanisms and new therapies for ER breast cancer. The knockout, 129S6/SvEvTac-Stat1 ( ), females develop luminal type FoxA1 , ER , and PR mammary carcinomas after prolonged latencies.

A Multicenter Study to Evaluate Diagnostic Accuracy by Pathologists Using the Aperio GT 450 DX in Local and Remote Viewing Stations.

Context.—: The adoption of digital pathology may enable pathologists to perform primary diagnosis in both local and remote whole slide image viewing settings, improving logistics and convenience.

Objective.

Intratumoral Injection of mRNA-2752 and Pembrolizumab for High-Risk Ductal Carcinoma In Situ: A Phase 1 Nonrandomized Clinical Trial.

Importance: Intratumoral immunotherapy that leverages the biological characteristics of high-risk ductal carcinoma in situ (DCIS) may be able to reduce the extent of surgical treatment and provide an alternative approach to improve patient outcomes.

Objective: To determine if combination intratumoral immunotherapy can activate immune cells to shrink or eliminate high-risk DCIS.

Design, Setting, And Participants: This phase 1 open-label nonrandomized clinical trial at a single academic center tested the safety and efficacy of intratumoral immunotherapy in patients with high-risk DCIS, defined as at least 2 of the following present: younger than 45 years, tumor size greater than 5 cm, high-grade, palpable mass, hormone receptor (HR)-negative, or ERBB2-positive.

Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner.

Identifying tumor-mediated mechanisms that impair immunity is instrumental for the design of new cancer therapies. Regulatory T cells (Tregs) are a key component of cancer-derived immune suppression; however, these lymphocytes are necessary to prevent systemic autoimmunity in mice and humans, and thus, direct targeting of Tregs is not a clinical option for cancer patients. We have previously demonstrated that excising transcription factor Kruppel-like factor 2 () within the T cell lineage blocks the generation of peripheral-derived Tregs (pTregs) without impairing production of thymic-derived Tregs.

Melanoma progression and prognostic models drawn from single-cell, spatial maps of benign and malignant tumors.

Melanoma clinical outcomes emerge from incompletely understood genetic mechanisms operating within the tumor and its microenvironment. Here, we used single-cell RNA-based spatial molecular imaging (RNA-SMI) in patient-derived archival tumors to reveal clinically relevant markers of malignancy progression and prognosis. We examined spatial gene expression of 203,472 cells inside benign and malignant melanocytic neoplasms, including melanocytic nevi and primary invasive and metastatic melanomas.

Nonlinear progression during the occult transition establishes cancer lethality.

Cancer screening is based upon a linear model of neoplastic growth and malignant progression. Yet, historical observations suggest that malignant progression is uncoupled from growth which may explain the paradoxical increase in early-stage breast cancer detection without a dramatic reduction in metastatic burden. Here we lineage trace millions of genetically transformed field cells and thousands of screen detectable and symptomatic tumors using a cancer rainbow mouse model of HER2+ breast cancer.

Engrailed-1 Promotes Pancreatic Cancer Metastasis.

Engrailed-1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Here, near-infrared auto-photoacoustic (NIRAPA) imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque.

Pituitary adenoma or neuroendocrine tumour: the need for an integrated prognostic classification.

In the 2022 fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, pituitary adenomas are reclassified as neuroendocrine tumours (NETs). This change confers an oncology label to neoplasms that are overwhelmingly benign. A comprehensive clinical classification schema is required to guide prognosis, therapy and outcomes for all patients with pituitary adenomas.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Photoacoustic imaging has sufficient penetration and sensitivity to map and characterize human atherosclerotic plaque.

Biochemical analyses of tau and other neuronal markers in the submandibular gland and frontal cortex across stages of Alzheimer disease.

Hyperphosphorylation of the microtubule-associated protein tau is hypothesized to lead to the development of neurofibrillary tangles in select brain regions during normal aging and in Alzheimer disease (AD). The distribution of neurofibrillary tangles is staged by its involvement starting in the transentorhinal regions of the brain and in final stages progress to neocortices. However, it has also been determined neurofibrillary tangles can extend into the spinal cord and select tau species are found in peripheral tissues and this may be depended on AD disease stage.

A Pilot Validation Study Comparing Fluorescence-Imitating Brightfield Imaging, A Slide-Free Imaging Method, With Standard Formalin-Fixed, Paraffin-Embedded Hematoxylin-Eosin-Stained Tissue Section Histology for Primary Surgical Pathology Diagnosis.

Context.—: Digital pathology using whole slide images has been recently approved to support primary diagnosis in clinical surgical pathology practices. Here we describe a novel imaging method, fluorescence-imitating brightfield imaging, that can capture the surface of fresh tissue without requiring prior fixation, paraffin embedding, tissue sectioning, or staining.

Biomarkers of Tumor Heterogeneity in Glioblastoma Multiforme Cohort of TCGA.

Tumor Whole Slide Images (WSI) are often heterogeneous, which hinders the discovery of biomarkers in the presence of confounding clinical factors. In this study, we present a pipeline for identifying biomarkers from the Glioblastoma Multiforme (GBM) cohort of WSIs from TCGA archive. The GBM cohort endures many technical artifacts while the discovery of GBM biomarkers is challenged because "age" is the single most confounding factor for predicting outcomes.

Convection and extracellular matrix binding control interstitial transport of extracellular vesicles.

Extracellular vesicles (EVs) influence a host of normal and pathophysiological processes in vivo. Compared to soluble mediators, EVs can traffic a wide range of proteins on their surface including extracellular matrix (ECM) binding proteins, and their large size (∼30-150 nm) limits diffusion. We isolated EVs from the MCF10 series-a model human cell line of breast cancer progression-and demonstrated increasing presence of laminin-binding integrins α3β1 and α6β1 on the EVs as the malignant potential of the MCF10 cells increased.

Identifying Good Candidates for Active Surveillance of Ductal Carcinoma : Insights from a Large Neoadjuvant Endocrine Therapy Cohort.

Unlabelled: Ductal carcinoma (DCIS) is a biologically heterogenous entity with uncertain risk for invasive ductal carcinoma (IDC) development. Standard treatment is surgical resection often followed by radiation. New approaches are needed to reduce overtreatment.

Social influences on physical activity for establishing criteria leading to exercise persistence.

Despite well-documented health benefits from exercise, a study on national trends in achieving the recommended minutes of physical activity guidelines has not improved since the guidelines were published in 2008. Peer interactions have been identified as a critical factor for increasing a population's physical activity. The objective of this study is for establishing criteria for social influences on physical activity for establishing criteria that lead to exercise persistence.

A Common Cell of Origin for Inflammatory Myofibroblastic Tumor and Lung Adenocarcinoma with ALK rearrangement.

This case signifies the importance of obtaining tumor comprehensive genomic profiling (CGP) as it has utility in cancer type classification and helping in diagnosing recurrence/metastasis or separately occurring primary tumors. CGP can also help guiding treatment as in this case separately occurring Inflammatory Myofibroblastic Tumor had ALK fusion and responded to crizotinib. As treatment progresses, new biopsies should be obtained and CGP used to evaluate for appearance of any new genomic alterations, in order to guide further therapy.

Standardizing Pathologic Evaluation of Breast Carcinoma After Neoadjuvant Chemotherapy.

Context.—: Neoadjuvant systemic therapy refers to the use of systemic agent(s) for malignancy prior to surgical treatment and has recently emerged as an option for most breast cancer patients eligible for adjuvant systemic therapy. Consequently, treated breast carcinomas have become routine specimens in pathology practices.

Mapping hormone-regulated cell-cell interaction networks in the human breast at single-cell resolution.

The rise and fall of estrogen and progesterone across menstrual cycles and during pregnancy regulates breast development and modifies cancer risk. How these hormones impact each cell type in the breast remains poorly understood because they act indirectly through paracrine networks. Using single-cell analysis of premenopausal breast tissue, we reveal a network of coordinated transcriptional programs representing the tissue-level response to changing hormone levels.

Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop NRF2 in cancer therapeutic resistance.

Metabolic and epigenetic reprogramming play important roles in cancer therapeutic resistance. However, their interplays are poorly understood. We report here that elevated TIGAR (TP53-induced glycolysis and apoptosis regulator), an antioxidant and glucose metabolic regulator and a target of oncogenic histone methyltransferase NSD2 (nuclear receptor binding SET domain protein 2), is mainly localized in the nucleus of therapeutic resistant tumor cells where it stimulates NSD2 expression and elevates global H3K36me2 mark.

Magnetic resonance imaging of tumor-associated-macrophages (TAMs) with a nanoparticle contrast agent.

In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment.