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  1. Article ; Online: Advanced Companion Diagnostics Facilities: Opportunity Favors the Prepared Laboratory.

    Gruver, Aaron M / Schade, Andrew E

    Archives of pathology & laboratory medicine

    2015  Volume 139, Issue 10, Page(s) 1201

    MeSH term(s) Humans ; Molecular Diagnostic Techniques/methods ; Molecular Targeted Therapy/methods ; Neoplasms/diagnosis ; Neoplasms/therapy
    Language English
    Publishing date 2015-10
    Publishing country United States
    Document type Comment ; Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 194119-7
    ISSN 1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
    ISSN (online) 1543-2165
    ISSN 0363-0153 ; 0096-8528 ; 0003-9985
    DOI 10.5858/arpa.2015-0095-LE
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Two Instrument Comparison of Reagents From a US FDA-Approved Assay for the Assessment of Ki-67 in High-Risk Early Breast Cancer.

    Komforti, Miglena / Downs-Kelly, Erinn / Sapunar, Francisco / Wijayawardana, Sameera R / Gruver, Aaron M / Badve, Sunil S

    Applied immunohistochemistry & molecular morphology : AIMM

    2022  Volume 30, Issue 8, Page(s) 577–583

    Abstract: The objective of this study was to measure concordance of results obtained from the US Food and Drug Administration-approved Ki-67 immunohistochemistry MIB-1 pharmDx assay performed on the Dako Omnis automated staining instrument (Omnis) versus results ... ...

    Abstract The objective of this study was to measure concordance of results obtained from the US Food and Drug Administration-approved Ki-67 immunohistochemistry MIB-1 pharmDx assay performed on the Dako Omnis automated staining instrument (Omnis) versus results produced from the assay reagents applied using an optimized protocol on the more widely available Autostainer Link 48 (ASL48) platform. Tissue sections obtained from 40 formalin-fixed paraffin-embedded breast carcinoma samples, with available Oncotype DX Breast Recurrence Score (RS) results, were stained. Three certified pathologists scored slides at 3 timepoints, totaling 360 observations for each instrument (N=720 total) using the approved scoring approach. Using the ≥20% cutoff, agreement was calculated with corresponding 2-sided 95% percentile bootstrap confidence intervals (CIs). Pairwise comparisons (N=360) from the interinstrument evaluation, performed with all observers, resulted in 325 (90.3%) concordant outcomes (244 negative and 81 positive) and 35 (9.7%) discordant outcomes. The overall agreement was 90.3% (95% confidence interval, 85.6% to 94.4%). No significant systematic differences were observed between instruments. Specimens scored from the Omnis were on average <1% higher than ASL48, with high correlation and little bias between the continuous Ki-67 scores (concordance correlation coefficient=0.916). Most specimens with a Ki-67 score ≥20% had a RS >25. This study demonstrated that good concordance can be achieved with the reagents run on the ASL48 instrument when using an optimized protocol and standardized scoring.
    MeSH term(s) Breast Neoplasms/diagnosis ; Female ; Humans ; Immunohistochemistry ; Indicators and Reagents ; Ki-67 Antigen ; United States ; United States Food and Drug Administration
    Chemical Substances Indicators and Reagents ; Ki-67 Antigen
    Language English
    Publishing date 2022-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1473273-7
    ISSN 1533-4058 ; 1062-3345 ; 1541-2016
    ISSN (online) 1533-4058
    ISSN 1062-3345 ; 1541-2016
    DOI 10.1097/PAI.0000000000001050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Population-based estimate for the correlation of the Oncotype Dx Breast Recurrence Score® result and Ki-67 IHC MIB-1 pharmDx in HR+, HER2-, node-positive early breast cancer.

    Crager, Michael / Wijayawardana, Sameera R / Gruver, Aaron M / Blacklock, Andrea / Russell, Christy / Baehner, Frederick L / Sapunar, Francisco

    Breast cancer research : BCR

    2022  Volume 24, Issue 1, Page(s) 74

    Abstract: Background: The United States Food and Drug Administration recently approved a Ki-67 immunohistochemistry (IHC) assay to identify patients with early breast cancer at high disease recurrence risk. The Oncotype Dx Breast Recurrence Score® assay has been ... ...

    Abstract Background: The United States Food and Drug Administration recently approved a Ki-67 immunohistochemistry (IHC) assay to identify patients with early breast cancer at high disease recurrence risk. The Oncotype Dx Breast Recurrence Score® assay has been validated in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) invasive breast cancer (IBC) to predict chemotherapy benefit and distant recurrence risk, regardless of nodal status. This study assessed the correlation between Recurrence Score® (RS) results and the Ki-67 IHC MIB-1 pharmDx assay.
    Methods: HR+, HER2-, N1 IBC samples with RS results were examined by Ki-67 IHC; 311 specimens were collected, including 275 without regard to RS ("unselected RS") and 36 more with RS 26-100; 12 were lymph node negative upon pathology report review, and one had no Ki-67 score, leaving 262 unselected RS and 298 total samples. Spearman rank correlation was calculated using the unselected samples and a weighted rank correlation using all samples. A receiver operating characteristic (ROC) curve for predicting high RS (26-100) from Ki-67 was constructed.
    Results: The Spearman rank correlation between Ki-67 and RS results was moderately positive (unselected RS samples: 0.396; 95% confidence interval [CI] 0.288-0.493; all samples: 0.394; 95% CI 0.294-0.486). While 71% of samples with RS 26-100 had Ki-67 ≥ 20%, 75% with RS 0-25 had Ki-67 < 20%. ROC area under the curve was 0.792 (95% CI 0.725-0.859).
    Conclusions: The moderately positive correlation is consistent with previous analyses suggesting the Oncotype Dx® assay and Ki-67 IHC MIB-1 assay should not be used interchangeably in clinical practice.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/pathology ; Immunohistochemistry ; Prognosis ; Neoplasm Recurrence, Local/pathology ; ROC Curve ; Biomarkers, Tumor/metabolism
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2022-11-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2015059-3
    ISSN 1465-542X ; 1465-5411
    ISSN (online) 1465-542X
    ISSN 1465-5411
    DOI 10.1186/s13058-022-01571-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Pathologist-trained machine learning classifiers developed to quantitate celiac disease features differentiate endoscopic biopsies according to modified marsh score and dietary intervention response.

    Gruver, Aaron M / Lu, Haiyan / Zhao, Xiaoxian / Fulford, Angie D / Soper, Michael D / Ballard, Darryl / Hanson, Jeffrey C / Schade, Andrew E / Hsi, Eric D / Gottlieb, Klaus / Credille, Kelly M

    Diagnostic pathology

    2023  Volume 18, Issue 1, Page(s) 122

    Abstract: Background: Histologic evaluation of the mucosal changes associated with celiac disease is important for establishing an accurate diagnosis and monitoring the impact of investigational therapies. While the Marsh-Oberhuber classification has been used to ...

    Abstract Background: Histologic evaluation of the mucosal changes associated with celiac disease is important for establishing an accurate diagnosis and monitoring the impact of investigational therapies. While the Marsh-Oberhuber classification has been used to categorize the histologic findings into discrete stages (i.e., Type 0-3c), significant variability has been documented between observers using this ordinal scoring system. Therefore, we evaluated whether pathologist-trained machine learning classifiers can be developed to objectively quantitate the pathological changes of villus blunting, intraepithelial lymphocytosis, and crypt hyperplasia in small intestine endoscopic biopsies.
    Methods: A convolutional neural network (CNN) was trained and combined with a secondary algorithm to quantitate intraepithelial lymphocytes (IEL) with 5 classes on CD3 immunohistochemistry whole slide images (WSI) and used to correlate feature outputs with ground truth modified Marsh scores in a total of 116 small intestine biopsies.
    Results: Across all samples, median %CD3 counts (positive cells/enterocytes) from villous epithelium (VE) increased with higher Marsh scores (Type 0%CD3 VE = 13.4; Type 1-3%CD3 VE = 41.9, p < 0.0001). Indicators of villus blunting and crypt hyperplasia were also observed (Type 0-2 villous epithelium/lamina propria area ratio = 0.81; Type 3a-3c villous epithelium/lamina propria area ratio = 0.29, p < 0.0001), and Type 0-1 crypt/villous epithelial area ratio = 0.59; Type 2-3 crypt/villous epithelial area ratio = 1.64, p < 0.0001). Using these individual features, a combined feature machine learning score (MLS) was created to evaluate a set of 28 matched pre- and post-intervention biopsies captured before and after dietary gluten restriction. The disposition of the continuous MLS paired biopsy result aligned with the Marsh score in 96.4% (27/28) of the cohort.
    Conclusions: Machine learning classifiers can be developed to objectively quantify histologic features and capture additional data not achievable with manual scoring. Such approaches should be further investigated to improve biopsy evaluation, especially for clinical trials.
    MeSH term(s) Humans ; Celiac Disease/diagnosis ; Celiac Disease/pathology ; Pathologists ; Hyperplasia/pathology ; Wetlands ; Biopsy/methods ; Intestinal Mucosa/pathology
    Language English
    Publishing date 2023-11-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2210518-9
    ISSN 1746-1596 ; 1746-1596
    ISSN (online) 1746-1596
    ISSN 1746-1596
    DOI 10.1186/s13000-023-01412-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone.

    Polewski, Monika D / Nielsen, Gitte B / Gu, Ying / Weaver, Aaron T / Gegg, Gavin / Tabuena-Frolli, Siena / Cajaiba, Mariana / Hanks, Debra / Method, Michael / Press, Michael F / Gottstein, Claudia / Gruver, Aaron M

    Applied immunohistochemistry & molecular morphology : AIMM

    2022  Volume 30, Issue 4, Page(s) 237–245

    Abstract: The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study ( ... ...

    Abstract The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed and validated for sensitivity, specificity, repeatability, precision, and robustness using a predefined ≥20% cutoff. Reproducibility studies (intersite and intrasite, interobserver and intraobserver) were conducted at 3 external laboratories using detailed scoring instructions designed for monarchE. Using the assay, patient tumors were classified as displaying high (≥20%) or low (<20%) Ki-67 expression; Kaplan-Meier methods evaluated 2-year invasive disease-free survival rates for these 2 groups among patients treated with endocrine therapy (ET) alone. All analytical validation and reproducibility studies achieved point estimates of >90% for negative, positive, and overall percent agreement. Intersite reproducibility produced point estimate values of 94.7%, 100.0%, and 97.3%. External interobserver reproducibility produced point estimate values of 98.9%, 97.8%, and 98.3%. Among 1954 patients receiving ET alone, 986 (50.5%) had high and 968 (49.5%) had low Ki-67 expression. Patients with high Ki-67 had a clinically meaningful increased risk of developing invasive disease within 2 years compared with those with low Ki-67 [2-y invasive disease-free survival rate: 86.1% (95% confidence interval: 83.1%-88.7%) vs. 92.0% (95% confidence interval: 89.7%-93.9%), respectively]. This standardized Ki-67 methodology resulted in high concordance across multiple laboratories, and its use in the monarchE study prospectively demonstrated the prognostic value of Ki-67 IHC in HR+, HER2- early breast cancer with high-risk clinicopathologic features.
    MeSH term(s) Biomarkers, Tumor/metabolism ; Breast Neoplasms/pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/metabolism ; Neoplasm Recurrence, Local ; Receptor, ErbB-2/metabolism ; Reproducibility of Results
    Chemical Substances Biomarkers, Tumor ; Ki-67 Antigen ; Receptor, ErbB-2 (EC 2.7.10.1)
    Language English
    Publishing date 2022-04-07
    Publishing country United States
    Document type Clinical Trial, Phase III ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1473273-7
    ISSN 1533-4058 ; 1062-3345 ; 1541-2016
    ISSN (online) 1533-4058
    ISSN 1062-3345 ; 1541-2016
    DOI 10.1097/PAI.0000000000001009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Targeted Quantitative Mass Spectrometry Analysis of Protein Biomarkers From Previously Stained Single Formalin-Fixed Paraffin-Embedded Tissue Sections.

    Ackermann, Bradley L / Morrison, Ryan D / Hill, Salisha / Westfall, Matthew D / Butts, Brent D / Soper, Michael D / Fill, Jeff A / Schade, Andrew E / Liebler, Daniel C / Gruver, Aaron M

    Laboratory investigation; a journal of technical methods and pathology

    2023  Volume 103, Issue 4, Page(s) 100052

    Abstract: Formalin-fixed, paraffin-embedded tissues represent a majority of all biopsy specimens commonly analyzed by histologic or immunohistochemical staining with adhesive coverslips attached. Mass spectrometry (MS) has recently been used to precisely quantify ... ...

    Abstract Formalin-fixed, paraffin-embedded tissues represent a majority of all biopsy specimens commonly analyzed by histologic or immunohistochemical staining with adhesive coverslips attached. Mass spectrometry (MS) has recently been used to precisely quantify proteins in samples consisting of multiple unstained formalin-fixed, paraffin-embedded sections. Here, we report an MS method to analyze proteins from a single coverslipped 4-μm section previously stained with hematoxylin and eosin, Masson trichrome, or 3,3'-diaminobenzidine-based immunohistochemical staining. We analyzed serial unstained and stained sections from non-small cell lung cancer specimens for proteins of varying abundance (PD-L1, RB1, CD73, and HLA-DRA). Coverslips were removed by soaking in xylene, and after tryptic digestion, peptides were analyzed by targeted high-resolution liquid chromatography with tandem MS with stable isotope-labeled peptide standards. The low-abundance proteins RB1 and PD-L1 were quantified in 31 and 35 of 50 total sections analyzed, respectively, whereas higher abundance CD73 and HLA-DRA were quantified in 49 and 50 sections, respectively. The inclusion of targeted β-actin measurement enabled normalization in samples where residual stain interfered with bulk protein quantitation by colorimetric assay. Measurement coefficient of variations for 5 replicate slides (hematoxylin and eosin stained vs unstained) from each block ranged from 3% to 18% for PD-L1, from 1% to 36% for RB1, 3% to 21% for CD73, and 4% to 29% for HLA-DRA. Collectively, these results demonstrate that targeted MS protein quantification can add a valuable data layer to clinical tissue specimens after assessment for standard pathology end points.
    MeSH term(s) Humans ; B7-H1 Antigen ; HLA-DR alpha-Chains ; Carcinoma, Non-Small-Cell Lung ; Paraffin Embedding/methods ; Hematoxylin ; Eosine Yellowish-(YS) ; Lung Neoplasms ; Proteins/metabolism ; Peptides ; Biomarkers ; Tandem Mass Spectrometry/methods ; Formaldehyde/chemistry ; Tissue Fixation
    Chemical Substances B7-H1 Antigen ; HLA-DR alpha-Chains ; Hematoxylin (YKM8PY2Z55) ; Eosine Yellowish-(YS) (TDQ283MPCW) ; Proteins ; Peptides ; Biomarkers ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1016/j.labinv.2022.100052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes, Cancer-Associated Fibroblasts, and CD200 in Pancreatic Cancer.

    MacNeil, Tyler / Vathiotis, Ioannis A / Shafi, Saba / Aung, Thazin Nwe / Zugazagoitia, Jon / Gruver, Aaron M / Driscoll, Kyla / Rimm, David L

    Cancers

    2021  Volume 13, Issue 21

    Abstract: Pancreatic cancer is marked by a desmoplastic tumor microenvironment and low tumor immunogenicity, making it difficult for immunotherapy drugs to improve outcomes for patients. Tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs) ...

    Abstract Pancreatic cancer is marked by a desmoplastic tumor microenvironment and low tumor immunogenicity, making it difficult for immunotherapy drugs to improve outcomes for patients. Tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs) are seen in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma (PDAC). In this work, we sought to characterize the expression levels and potential prognostic value of TILs (CD4, CD8, and CD20) and CAFs (Thy-1, FAP, and SMA) in a large retrospective cohort of PDAC patients. Additionally, we investigated the expression levels and prognostic significance of CD200, an immunoinhibitory protein that has shown interest as a potential target for immune checkpoint blockade. We measured the expression levels of these seven proteins with multiplexed immunofluorescence staining and quantitative immunofluorescence (QIF). We found CD8 and FAP to be independent predictors of progression-free survival and overall survival. CD200 was found to be heterogeneously expressed in both the tumor and stromal compartments of PDAC, with the majority of patients having positive stromal expression and negative tumor expression. This work demonstrates the potential clinical utility of CD8 and FAP in PDAC patients, and it sheds light on the expression patterns of CD200 in pancreatic cancer as the protein is being tested as a target for immune checkpoint blockade.
    Language English
    Publishing date 2021-11-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13215501
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  8. Article: Quantitative Assessment of CD200 and CD200R Expression in Lung Cancer.

    Vathiotis, Ioannis A / MacNeil, Tyler / Zugazagoitia, Jon / Syrigos, Konstantinos N / Aung, Thazin Nwe / Gruver, Aaron M / Vaillancourt, Peter / Hughes, Ina / Hinton, Steve / Driscoll, Kyla / Rimm, David L

    Cancers

    2021  Volume 13, Issue 5

    Abstract: CD200/CD200R is an immune checkpoint with broad expression patterns and a potential target for immune therapy. In this study, we assess both CD200 and CD200R expression in solid tumors, with a focus on lung cancer, and evaluate their association with ... ...

    Abstract CD200/CD200R is an immune checkpoint with broad expression patterns and a potential target for immune therapy. In this study, we assess both CD200 and CD200R expression in solid tumors, with a focus on lung cancer, and evaluate their association with clinicopathologic characteristics, mutation status, outcome, and programmed death-ligand 1 (PD-L1) expression. We used multiplexed quantitative immunofluorescence (QIF) to measure the expression of CD200 and CD200R in a total of 455 patients from three lung cancer cohorts. Using carefully validated antibodies, we performed target measurement with tyramide-based QIF panels and analyzed the data using the PM2000 microscope and AQUA software. CD200 tumor positivity was found in 29.7% of non-small cell lung cancer (NSCLC) patients and 33.3% of lung large cell neuroendocrine carcinoma (LCNEC) patients. CD200 demonstrated notable intratumoral heterogeneity. CD200R was expressed in immune cells in 25% of NSCLC and 41.3% of LCNEC patients. While CD200R is predominantly expressed in immune cells, rare tumor cell staining was seen in a highly heterogeneous pattern. CD200R expression in the stromal compartment was significantly higher in patients with squamous differentiation (
    Language English
    Publishing date 2021-03-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13051024
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  9. Article ; Online: Proteomic characterisations of ulcerative colitis endoscopic biopsies associate with clinically relevant histological measurements of disease severity.

    Gruver, Aaron M / Westfall, Matt D / Ackermann, Bradley L / Hill, Salisha / Morrison, Ryan D / Bodo, Juraj / Lai, Keith K / Gemperline, David C / Hsi, Eric D / Liebler, Daniel C / Schmitz, Jochen / Benschop, Robert J

    Journal of clinical pathology

    2021  Volume 75, Issue 9, Page(s) 636–642

    Abstract: Aims and methods: Accurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ...

    Abstract Aims and methods: Accurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies.
    Results: Targeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R
    Conclusions: Pathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach.
    MeSH term(s) Biopsy ; Colitis, Ulcerative/pathology ; Colonoscopy ; Humans ; Interleukin-23 ; Intestinal Mucosa/pathology ; Proteomics ; Severity of Illness Index
    Chemical Substances Interleukin-23
    Language English
    Publishing date 2021-08-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 80261-x
    ISSN 1472-4146 ; 0021-9746
    ISSN (online) 1472-4146
    ISSN 0021-9746
    DOI 10.1136/jclinpath-2021-207718
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  10. Article ; Online: Accelerated instability testing reveals quantitative mass spectrometry overcomes specimen storage limitations associated with PD-L1 immunohistochemistry.

    Haragan, Alexander / Liebler, Daniel C / Das, Dimple M / Soper, Michael D / Morrison, Ryan D / Slebos, Robbert J C / Ackermann, Bradley L / Fill, Jeff A / Schade, Andrew E / Gosney, John R / Gruver, Aaron M

    Laboratory investigation; a journal of technical methods and pathology

    2020  Volume 100, Issue 6, Page(s) 874–886

    Abstract: Immunohistochemistry (IHC) using formalin-fixed, paraffin embedded (FFPE) tissue is limited by epitope masking, posttranslational modification and immunoreactivity loss that occurs in stored tissue by poorly characterized mechanisms. Conformational ... ...

    Abstract Immunohistochemistry (IHC) using formalin-fixed, paraffin embedded (FFPE) tissue is limited by epitope masking, posttranslational modification and immunoreactivity loss that occurs in stored tissue by poorly characterized mechanisms. Conformational epitopes recognized by many programmed-death-ligand-1 (PD-L1) IHC assays are particularly susceptible to degradation and provide an ideal model for understanding signal loss in stored FFPE tissue. Here we assessed 1206 tissue sections to evaluate environmental factors impacting immunoreactivity loss. PD-L1 IHC using four antibodies (22C3, 28-8, E1L3N, and SP142), raised against intracellular and extracellular epitopes, was assessed in stored FFPE tissue alongside quantitative mass spectrometry (MS). Global proteome analyses were used to assess proteome-wide oxidation across an inventory of 3041 protein groups (24,737 distinct peptides). PD-L1 quantitation correlated well with IHC expression on unaged sections (R
    MeSH term(s) B7-H1 Antigen/analysis ; B7-H1 Antigen/chemistry ; Humans ; Immunohistochemistry/methods ; Mass Spectrometry/methods ; Neoplasms/chemistry ; Proteome/analysis ; Proteome/chemistry ; Proteomics/methods ; Specimen Handling
    Chemical Substances B7-H1 Antigen ; CD274 protein, human ; Proteome
    Language English
    Publishing date 2020-01-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1038/s41374-019-0366-y
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