Publications by authors named "Jennifer M Yoest"

4 Publications

  • Page 1 of 1

A Next-Generation Sequencing Test for Severe Congenital Neutropenia: Utility in a Broader Clinicopathologic Spectrum of Disease.

J Mol Diagn 2021 Feb 17;23(2):200-211. Epub 2020 Nov 17.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. Electronic address:

Severe congenital neutropenia (SCN) is a collection of diverse disorders characterized by chronically low absolute neutrophil count in the peripheral blood, increased susceptibility to infection, and a significant predisposition to the development of myeloid malignancies. SCN can be acquired or inherited. Inherited forms have been linked to variants in a group of diverse genes involved in the neutrophil-differentiation process. Variants that promote resistance to treatment have also been identified. Thus, genetic testing is important for the diagnosis, prognosis, and management of SCN. Herein we describe clinically validated assay developed for assessing patients with suspected SCN. The assay is performed from a whole-exome backbone. Variants are called across all coding exons, and results are filtered to focus on 48 genes that are clinically relevant to SCN. Validation results indicated 100% analytical sensitivity and specificity for the detection of constitutional variants among the 48 reportable genes. To date, 34 individuals have been referred for testing (age range: birth to 67 years). Several pathogenic and likely pathogenic variants have been identified, including one in a patient with late-onset disease. The pattern of cases referred for testing suggests that this assay has clinical utility in a broader spectrum of patients beyond those in the pediatric population who have classic early-onset symptoms characteristic of SCN.
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http://dx.doi.org/10.1016/j.jmoldx.2020.10.014DOI Listing
February 2021

Sequencing-Based Measurable Residual Disease Testing in Acute Myeloid Leukemia.

Front Cell Dev Biol 2020 8;8:249. Epub 2020 May 8.

Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, United States.

Next generation sequencing (NGS) methods have allowed for unprecedented genomic characterization of acute myeloid leukemia (AML) over the last several years. Further advances in NGS-based methods including error correction using unique molecular identifiers (UMIs) have more recently enabled the use of NGS-based measurable residual disease (MRD) detection. This review focuses on the use of NGS-based MRD detection in AML, including basic methodologies and clinical applications.
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http://dx.doi.org/10.3389/fcell.2020.00249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225302PMC
May 2020

Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review.

Authors:
Jennifer M Yoest

Immunotargets Ther 2017 10;6:73-82. Epub 2017 Oct 10.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Identification and characterization of T-cell regulatory mechanisms, or checkpoints, have led to a wave of drug development aimed at inhibiting these targets to "remove the brakes" of the immune system. This class of anticancer therapeutics, termed immune checkpoint inhibitors (ICIs), has harnessed the potential of the body's own immune system to recognize cancerous cells and selectively eliminate them, in some cases with alarming success. This new breakthrough, however, has not been without its drawbacks. Immune-related adverse events (irAEs) are adverse events encountered during treatment with ICIs that are thought to be mediated through the patient's immune system which can manifest with a variety of symptoms which often resemble autoimmunity. These events range widely in presentation and severity and are reported frequently. Here, we will discuss a large selection of case reports in order to inform the clinician, laboratorian, and researcher of the scope of organ systems affected, the severity of the conditions being encountered, and the responses of these events to treatment, as well as explore the use of ICIs in the setting of preexisting autoimmunity. We will also consider the ability to detect autoantibodies before and during irAEs as well as the correlations that irAEs have with clinical outcomes. Finally, we will conclude by exploring the possibility that two distinct pathways may be contributing to the phenomenon of irAEs within this class of drugs, and the role that this might play in future research and clinical practice.
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http://dx.doi.org/10.2147/ITT.S126227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644546PMC
October 2017

Effects of Hydrochloric Acid and Formic Acid Decalcification on Breast Tumor Biomarkers and HER2 Fluorescence In Situ Hybridization.

Appl Immunohistochem Mol Morphol 2019 03;27(3):223-230

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA.

Biomarker analysis of metastatic breast carcinoma (MBC) is routinely recommended by ASCO/CAP guidelines, and establishing a diagnosis of MBC often requires immunohistochemistry (IHC). The reliability of breast tumor biomarkers and breast-specific markers on decalcified tissues has not been extensively studied. We performed IHC studies on breast tumors exposed to hydrochloric acid (HCl) and formic acid (FA) decalcification solutions, and HER2 fluorescence in situ hybridization on a subset of these tumors to establish a protocol for handling bone specimens with suspicion for MBC. Fifteen fresh cases of primary breast carcinoma and 8 HER2+ paraffin-embedded core biopsy cases were studied. Fresh tissue was divided into 5 fragments to approximate a bone core biopsy. One fragment (control) was fixed in 10% neutral buffered formalin. The remaining fragments were also exposed to FA or HCl decalcification for 1 or 5 hours. All fragments were embedded in 1 block and tested with an IHC panel. The known HER2+ cases were exposed to either 1 or 5 hours of FA, and HER2 fluorescence in situ hybridization was also performed. Results were interpreted as follows: H-scores for estrogen receptor, progesterone receptor, and GATA-3 were assigned from 0 to 300; HER2, cytokeratin 7, gross cystic disease fluid protein-15, Pax-8, TTF-1, cytokeratin 20, and mammaglobin were scored from 0 to 3+; and Ki67 from 0% to 100%. Mean scores were compared using the t test or Wilcoxon test for paired samples. No significant differences in mean score were seen between NF and 1 hour FA for any IHC immunoreactivity. After 5 hours of FA, only Ki67 average score was significantly less than NF. Mean scores for estrogen receptor, progesterone receptor, HER2, Ki67, and GATA-3 were significantly lower than NF in the tissue after either 1 or 5 hours of HCl. Mean scores for gross cystic disease fluid protein-15, mammaglobin, and cytokeratin 7 staining were not significantly lower than NF after 1 or 5 hours of HCl.
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http://dx.doi.org/10.1097/PAI.0000000000000564DOI Listing
March 2019