Laboratory Investigation最新文献

{"title":"Corrigendum to “Epstein-Barr Virus–Encoded Latent Membrane Protein 2A Promotes Immune Escape by Upregulating SYK/Nuclear Factor-κB Signaling in Diffuse Large B-cell Lymphoma” [Laboratory Investigation 105 (2025) 104104]","authors":"Xiang-Nan Jiang , Dong Sheng , Wan-Hui Yan , Xiao-Jie Li , Qing-Xin Xia , Xiao-Qiu Li","doi":"10.1016/j.labinv.2025.104164","DOIUrl":"10.1016/j.labinv.2025.104164","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 5","pages":"Article 104164"},"PeriodicalIF":5.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOBEC Driven Hypermutation in the Lymphocyte-Predominant Group of Triple-Negative Breast Cancer.","authors":"Miseon Lee, Ahwon Lee, Tae-Kyung Yoo, Byung Joo Chae, Sung Gwe Ahn, Byung-Ock Choi, Woo-Chan Park, Sung Hun Kim, Jieun Lee, Jun Kang","doi":"10.1016/j.labinv.2025.104165","DOIUrl":"https://doi.org/10.1016/j.labinv.2025.104165","url":null,"abstract":"<p><p>This study aimed to evaluate the clinicopathologic and genomic characteristics of triple-negative breast cancer (TNBC) subclassification. TNBC was classified into the luminal androgen receptor (LAR) subtype and the tumor-infiltrating lymphocytes (TILs) groups of the non-LAR subtype-lymphocyte-predominant (LP), lymphocyte-intermediate (LI), and lymphocyte-depleted (LD)-based on androgen receptor immunohistochemistry and TILs. Clinicopathologic and genomic characteristics were evaluated for these TNBC subclasses. The LP group was associated with a histologic type of carcinoma with medullary features, a higher tumor mutation burden, and increased APOBEC activity, indicative of APOBEC-driven hypermutation. The LAR subtype was characterized by a higher prevalence of PIK3CA mutations, lower homologous recombination deficiency scores, and associations with histologic types of invasive lobular carcinoma, and carcinoma with apocrine differentiation. This study demonstrates the distinct clinicopathologic and genomic characteristics of TNBC subclassifications. APOBEC activity-related hypermutation is a defining characteristic of the LP group.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"104165"},"PeriodicalIF":5.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden in the Absence: Clinicopathologic Insights on Kidney Diseases Associated With Selective IgA Deficiency","authors":"Bangchen Wang ,&nbsp;Harpreet Singh ,&nbsp;Matthew Ellis ,&nbsp;Laura Barisoni ,&nbsp;David N. Howell","doi":"10.1016/j.labinv.2025.104163","DOIUrl":"10.1016/j.labinv.2025.104163","url":null,"abstract":"<div><div>Selective IgA deficiency (sIgAD) is the most common type of primary immunodeficiency. The diagnosis of sIgAD has occasionally been suggested when a complete absence of background IgA immunofluorescent staining on renal biopsies was observed, but such findings have been described in only 2 patients to date. In this study, the clinical, demographic, and renal biopsy findings of 15 patients with suspected sIgAD, based on a total lack of immunofluorescence for IgA, were collected. In our cohort, most patients presented with acute kidney injury, with or without proteinuria, and had clinical histories consistent with sIgAD, including recurrent infections, autoimmune diseases, allergic disorders, and cancer. However, only 1 patient had a known history of sIgAD. Immunoglobulin testing was available in 10 of 15 patients, 9 of whom showed findings consistent with a diagnosis of sIgAD. Renal biopsies in most patients revealed immune-related glomerular diseases, with lupus nephritis being the most common diagnosis. Recognizing the total absence of IgA staining indicative of sIgAD is important because it can be associated with recurrent infections, autoimmune diseases, allergic disorders, anaphylactic transfusion reactions, and, rarely, malignancies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 7","pages":"Article 104163"},"PeriodicalIF":5.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"","doi":"10.1016/S0023-6837(25)00042-X","DOIUrl":"10.1016/S0023-6837(25)00042-X","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 4","pages":"Article 104132"},"PeriodicalIF":5.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Therapy–Associated CDX2 Expression and Its Prognostic Implication in Esophageal Adenocarcinoma","authors":"Heong Ahn ,&nbsp;Madhurya Ramineni ,&nbsp;Hangchuan Shi ,&nbsp;Rena X. Li ,&nbsp;Moises Velez ,&nbsp;Yansheng Hao","doi":"10.1016/j.labinv.2025.104135","DOIUrl":"10.1016/j.labinv.2025.104135","url":null,"abstract":"<div><div>Neoadjuvant chemoradiotherapy followed by surgery is the standard care for locally advanced esophageal adenocarcinoma. However, reliable postoperative prognostic biomarkers are still needed to stratify patients with different clinical outcomes. This study aimed to investigate postneoadjuvant expression changes of CDX2 and its association with histopathological features, biomarkers for targeted therapy, distant metastasis, and survival status. A total of 62 esophagogastrectomy specimens from one institution were evaluated. A tissue microarray was constructed, and IHC staining was performed. CDX2 expression was found in 27 (43.5%) cases with well-to-poor differentiation. Compared with preoperative biopsies, 68.8% of cases demonstrated induced or enhanced CDX2 expression. There were no significant differences in age, tumor location, histologic grade, lymph node metastasis, tumor stage, and treatment response between CDX2-positive and CDX2-negative groups. Neuroendocrine and Paneth cell differentiation induced by neoadjuvant therapy were more commonly seen in CDX2-positive cases. CDX2 expression was associated with higher multidrug resistance-1 and HER-2 expression. Patients with CDX2-positive diseases showed a higher risk of distant metastasis and a worse prognosis than those with CDX2-negative diseases.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104135"},"PeriodicalIF":5.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Analysis of Factors Affecting Human Epidermal Growth Factor Receptor 2 Interpretation Consistency: Staining Protocols, Artificial Intelligence–Based Image Standardization, and Classification Criteria","authors":"Chen Jiang ,&nbsp;Mei Li ,&nbsp;Chengyou Zheng ,&nbsp;Shumei Yan ,&nbsp;Lingzhi Kong ,&nbsp;Yu Wu ,&nbsp;Jinhui Zhang ,&nbsp;Xue Chao ,&nbsp;Xi Cai ,&nbsp;Wentai Feng ,&nbsp;Jiehua He ,&nbsp;Rongzhen Luo ,&nbsp;Shuoyu Xu ,&nbsp;Yuanzhong Yang ,&nbsp;Peng Sun","doi":"10.1016/j.labinv.2025.104134","DOIUrl":"10.1016/j.labinv.2025.104134","url":null,"abstract":"<div><div>The efficacy of human epidermal growth factor receptor 2 (HER2)–targeting antibody-drug conjugates has underscored the critical need for precise HER2 diagnostics in breast cancer treatment. Despite the clinical importance, variability in immunohistochemical (IHC) staining protocols and interobserver inconsistencies challenge the reliability of HER2 status assessment, which is critical for guiding patient treatment strategies. To investigate the factors affecting HER2 interpretation consistency, tissue microarrays from 1063 breast carcinoma cases underwent 3 distinct IHC protocols, and a novel artificial intelligence (AI) model was developed to standardize HER2-stained images. A total of 5 sets of tissue microarrays (Nordi QC, protocol 1, protocol 2, protocol 1 AI, and protocol 2 AI) were independently reviewed by 8 pathologists. The Fleiss Kappa value and overall agreement rate measured interobserver agreement, with logistic regression analyzing the impact of variables on diagnostic accuracy. Our results showed that the Nordi QC protocol had the highest interobserver agreement (Kappa 0.754). AI-based image normalization notably enhanced consistency, particularly for HER2 low cases, aligning scores toward the Nordi QC standard. Logistic regression analysis indicated that both staining protocol and AI-based image standardization significantly influenced diagnostic accuracy (<em>P</em> &lt; .001). The American Society of Clinical Oncology/College of American Pathologists 2018 binary criteria demonstrated the highest HER2 interobserver consistency (Kappa &gt; 0.95). Compared with the American Society of Clinical Oncology/College of American Pathologists 2023 criteria, the newly proposed null, ultra-low/low, positive criteria, merging HER2 low and ultra-low categories, demonstrated improved reliability and agreement, especially in distinguishing the challenging HER2–ultra-low cases, which showed an exceedingly low interobserver agreement (Kappa &lt; 0.20) across all protocols. Overall, variability in IHC staining protocols and HER2 classification criteria significantly affect the diagnostic consistency among pathologists. The integration of an AI model for image standardization and the adoption of the null, ultra-low/low, positive criteria may refine diagnostic precision and bolster clinical decision-making in breast cancer treatment.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104134"},"PeriodicalIF":5.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibodies From Children With Acute Kawasaki Disease Identify a Common Antigenic Target in Fatal Cases Over 5 Decades","authors":"Anne H. Rowley ,&nbsp;Robert Byrd ,&nbsp;David Arrollo ,&nbsp;Amornrat O’Brien ,&nbsp;Stanford Shulman ,&nbsp;Masaru Terai ,&nbsp;Kwang-Youn Kim ,&nbsp;Kassandra Mercado ,&nbsp;Kristine Wylie ,&nbsp;Robert Fialkowski ,&nbsp;Susan C. Baker","doi":"10.1016/j.labinv.2025.104131","DOIUrl":"10.1016/j.labinv.2025.104131","url":null,"abstract":"<div><div>Kawasaki disease (KD) is a unique febrile illness of young children that can result in coronary artery aneurysms, myocardial infarction, aneurysm rupture, and sudden death. The epidemiologic features, including the young age group affected, the rarity of recurrence, and the presence of epidemics and outbreaks, point to a single infectious causative agent. The recent decrease in KD cases worldwide during pandemic mitigation supports transmission of the agent via a respiratory route. However, substantial research over decades has shown that KD etiology cannot be linked to any currently known infectious agent. We previously identified the presence of intracytoplasmic inclusion (ICI) bodies in the bronchial epithelium in children with fatal KD and a convergent plasmablast-derived antibody response to a specific protein epitope, supporting 1 predominant respiratory causative agent. Here, we report immunohistochemistry and epitope binding using an expanded pool of KD monoclonal antibodies prepared from single peripheral blood plasmablasts from 12 children with acute KD. We identified 1 or more monoclonal antibodies from each of the 12 patients that recognized ICI bodies in KD bronchial epithelium. Using a representative monoclonal antibody, ICI bodies were detected in 20 of 20 children with fatal KD across 5 decades, 10 from the United States and 10 from Japan, and were absent in 19 of 20 infant controls (<em>P</em> &lt; .001). We also found that all 12 children with acute KD generated plasmablast(s) recognizing the previously reported peptide antigen. Taken together, these results point to 1 predominant causative agent of KD across many decades and geographic areas and should direct future KD research studies.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104131"},"PeriodicalIF":5.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Virtual Tissue Microarrays for Validating Digital Biomarker Analysis in Colorectal Carcinoma” (Lab Invest 105(2025) 104098)","authors":"Margarita Melnikova Jørgensen ,&nbsp;Stephen Jacques Hamilton-Dutoit ,&nbsp;Jesper Bertram Bramsen ,&nbsp;Claus Lindbjerg Andersen ,&nbsp;Ida Elisabeth Holm","doi":"10.1016/j.labinv.2025.104122","DOIUrl":"10.1016/j.labinv.2025.104122","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 5","pages":"Article 104122"},"PeriodicalIF":5.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Correlation of the Extracellular Matrix to Immune Cell Phenotypes in the Tumor Boundary of Clear Cell Renal Cell Carcinoma Revealed by Cyclic Immunohistochemistry","authors":"Grigor Andreev ,&nbsp;Tino Vollmer ,&nbsp;Max Zirngibl ,&nbsp;Martin Werner ,&nbsp;Markus Grabbert ,&nbsp;Oliver Schilling ,&nbsp;Manuel Rogg ,&nbsp;Christoph Schell","doi":"10.1016/j.labinv.2025.104130","DOIUrl":"10.1016/j.labinv.2025.104130","url":null,"abstract":"<div><div>The significance of the tumor microenvironment (TME) in predicting immunotherapy efficacy is increasingly acknowledged. However, the complexity of the TME necessitates novel technological approaches for the precise characterization of individual cell types, functional phenotypes, and heterocellular spatial interactions. This study utilizes a streamlined multiplex cyclic immunohistochemistry (cycIHC) protocol for detailed TME annotation. Unlike proprietary methods, cycIHC relies on iterative cycles of conventional immunohistochemistry, using off-the-shelf antibodies and reagents, followed by digitalization, chromogen removal, and antibody stripping. The method was combined with open-source tools for the coregistration of individual staining cycles. Using clear cell renal cell carcinoma (ccRCC) as a model, the protocol was applied for granular annotation of cellular and acellular structures in the tumor boundary zone. Our results demonstrate that the tumor periphery, particularly the pseudocapsule of ccRCC, is homogeneously organized across the 3D scale, yet exhibits distinct cellular distribution gradients of T and B cells. These patterns correspond to deposited extracellular matrix proteins, especially collagen types I and VI. Our findings indicate an instructive impact of extracellular matrix proteins on defining the spatial organization of immune cells in the TME of ccRCC. The developed cycIHC method facilitates detailed characterization of the TME and may enhance the understanding of tumor-immune cell interactions.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104130"},"PeriodicalIF":5.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathology Education for Undergraduate and Graduate Students: It is Not Just for Clinical Trainees","authors":"Avrum I. Gotlieb ,&nbsp;Richard N. Mitchell","doi":"10.1016/j.labinv.2025.104126","DOIUrl":"10.1016/j.labinv.2025.104126","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 5","pages":"Article 104126"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}