Laboratory Investigation最新文献

{"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}

{"title":"Hepatoma-Derived Growth Factor Promotes Liver Carcinogenesis by Inducing Phosphatase and Tensin Homolog Inactivation","authors":"Shih-Ming Yang ,&nbsp;Tsung-Hui Hu ,&nbsp;Jian-Ching Wu ,&nbsp;Li-Na Yi ,&nbsp;Hsiao-Mei Kuo ,&nbsp;Mei-Lang Kung ,&nbsp;Tian-Huei Chu ,&nbsp;Shih-Tsung Huang ,&nbsp;Chao-Cheng Huang ,&nbsp;Ying-Hsien Kao ,&nbsp;Yu-Wei Lin ,&nbsp;Ming-Hong Tai","doi":"10.1016/j.labinv.2025.104127","DOIUrl":"10.1016/j.labinv.2025.104127","url":null,"abstract":"<div><div>Hepatoma-derived growth factor (HDGF) is located on chromosome 1q21-23, a locus frequently amplified in hepatocellular carcinoma (HCC), and has been proposed as an oncogenic factor by stimulating PI3K/Akt signaling. Phosphatase and tensin homolog (PTEN) acts as a tumor suppressor that antagonizes PI3K/Akt signaling, suggesting a possible regulatory effect of HDGF on PTEN. In this study, we aimed to investigate the regulatory role of HDGF on PTEN. The Cancer Genome Atlas cohort study was used to explore molecular significance and outcomes in liver cancer. Resected clinical specimens, consisting of paired tumor and adjacent nontumor tissue, were analyzed for expression of HDGF and PTEN in the liver cancer cohort. Liver tissue and primary hepatocytes derived from HDGF knockout mice were analyzed for PTEN status. The influence of HDGF on PTEN was investigated through in vitro and in vivo genetic manipulation studies. The Cancer Genome Atlas cohort study revealed an inverse correlation between HDGF and PTEN, with HDGF overexpression emerging as a dominant factor independent of PTEN levels and correlated with poor outcomes in patients with HCC. Paired clinical specimens revealed HDGF upregulation in tumor tissue is relevant to elevated alpha-fetoprotein, and poor survival and recurrent outcomes in the liver cancer cohort. HDGF knockout mice exhibited decreased liver C-tail--phosphorylated PTEN (p-PTEN) levels and increased PTEN expression. Furthermore, an in vitro study validated that overexpression of HDGF increased p-PTEN levels and tumor growth, whereas knockdown of HDGF yielded inverse results. Treatment with recombinant HDGF confirmed the stimulation of p-PTEN and accumulation of phosphatidylinositol 3,4,5-trisphosphate. Blockade of HDGF and casein kinase 2 signaling using anti-HDGF and a casein kinase 2 inhibitor validated the stimulation of p-PTEN. Our results reveal that <em>HDGF</em> is an oncogene frequently amplified and upregulated, leading to suppression of PTEN expression and activity, thereby contributing to malignant progression in liver cancer. HDGF upregulation in resected paired-HCC specimens may constitute a valuable prognostic biomarker for patients with HCC.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104127"},"PeriodicalIF":5.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625455","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":"Clinicopathological Characteristics of a Distinct Tumor Phenotype: Invasive Lobular Carcinoma With Tubular Elements in the West German Study Group ADAPTcycle Trial","authors":"Martin Radner ,&nbsp;Sandy Burmeister ,&nbsp;Katarzyna Jóźwiak ,&nbsp;Nora Schaumann ,&nbsp;Malte Gronewold ,&nbsp;Mieke Raap ,&nbsp;Stephan Bartels ,&nbsp;Henriette Christgen ,&nbsp;Leonie D. Kandt ,&nbsp;Pia Hillmann ,&nbsp;Ulrich Lehmann ,&nbsp;Oleg Gluz ,&nbsp;Monika Graeser ,&nbsp;Sherko Kümmel ,&nbsp;Christine zu Eulenburg ,&nbsp;Nadia Harbeck ,&nbsp;Hans Kreipe ,&nbsp;Matthias Christgen","doi":"10.1016/j.labinv.2025.104125","DOIUrl":"10.1016/j.labinv.2025.104125","url":null,"abstract":"<div><div>Invasive lobular carcinoma with tubular elements (ILC-TE) is a recently identified variant of invasive lobular breast carcinoma (ILC). The histology of ILC-TE is defined by noncohesive carcinoma cells mixed with cohesive tubular elements and complete loss of epithelial (E)-cadherin. Cell–cell adhesion is partially restored by switching from an E-cadherin–deficient to a placental (P)-cadherin–proficient status (EPS). The prevalence of ILC-TE remains unknown. Here, we report data from the central pathology review of &gt;4500 hormone receptor–positive/HER2-negative breast cancer (BC) cases recruited to the West German Study Group (WSG) ADAPTcycle trial (NCT04055493). The central pathology review included prospective assessment of BC types, variants, and E-cadherin expression. Cases classified as ILC-TE were analyzed for their molecular features and clinicopathological characteristics. Pure ILC with complete loss of E-cadherin accounted for 630 of 4619 (13.6%) BC cases. ILC-TE accounted for 47 of 630 (7.5%) lobular carcinomas, making it more than twice as prevalent as mixed BC (NST/ILC). ILC-TE harbored deleterious <em>CDH1</em>/E-cadherin mutations in 27 of 35 (77%) cases tested. EPS was detected in 43 of 47 (91%) ILC-TE cases. EPS was significantly more common in ILC-TE than in classic ILC or other ILC variants (<em>P</em> &lt; .001). Clinically, ILC-TE was associated with cT1 stage (<em>P</em> = .023), cN0 status (<em>P</em> = .024), lower histologic grade (<em>P</em> = .004), and lower Ki67 (<em>P</em> = .012). In contrast, solid ILC was associated with higher Ki67 (<em>P</em> = .006). Following preoperative endocrine therapy, higher post–preoperative endocrine therapy Ki67 levels were observed in trabecular ILC, solid-papillary ILC, and pleomorphic ILC (<em>P</em> &lt; .001, <em>P</em> = .006, and <em>P</em> = .021, respectively). In summary, ILC-TE is a quite common ILC variant that is associated with EPS, less-aggressive clinical features, and slow growth.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104125"},"PeriodicalIF":5.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573401","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":"Development of a Technique for Diagnosis and Screening of Superficial Bladder Cancer by Cell-Pellet DNA From Urine Sample","authors":"Jaekwon Seok ,&nbsp;Hee Jeong Kwak ,&nbsp;Chan-Koo Kang ,&nbsp;Ah Ram Kim ,&nbsp;Woo Suk Choi ,&nbsp;Hyoung Keun Park ,&nbsp;Sung Hyun Paick ,&nbsp;Hyeong Gon Kim ,&nbsp;Yeonjoo Kwak ,&nbsp;Tak-Il Jeon ,&nbsp;Kyung Min Lim ,&nbsp;Baeckseung Lee ,&nbsp;Aram Kim ,&nbsp;Ssang-Goo Cho","doi":"10.1016/j.labinv.2025.104124","DOIUrl":"10.1016/j.labinv.2025.104124","url":null,"abstract":"<div><div>Bladder cancer (BCa) is the most common malignancy of the urinary system with high incidence and recurrence rates. There are several ways to detect BCa. However, different approaches have different accuracy, which essentially depends on the sensitivity and specificity of the technique. Alternative noninvasive diagnostic tools for BCa are needed. We isolated and compared urinary cell-pellet DNA (cpDNA), cell-free DNA, and exosomal DNA from patients with localized BCa. Consequently, we analyzed 12 tissues and cpDNA samples by next-generation sequencing and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and noncoding sequences. Then, cpDNA and tissue DNA from 12 patients were analyzed using next-generation sequencing to verify that the genomic characteristics of cpDNA are concordant with those of tissue. We also detected somatic mutation patterns between tissues and their corresponding cpDNA samples. An overlapping variant analysis was performed based on somatic mutation data and a high similarity was observed. Moreover, we identified frequently mutated signaling pathways. In these results, several point mutations were analyzed in <em>FGFR3</em>, <em>TTN</em>, and <em>LEPROTL1</em> from the cpDNA of patients with BCa. Tumor mutational burden analysis showed that cpDNA had no significant difference in tumor mutational burden compared with tumor tissue. These results provide that cpDNA is a potential diagnostic source for detecting and managing BCa using alternative noninvasive methods from patient urine. Our findings may serve as a clinical tool for early detection or recurrence screening of nonmuscle invasive BCa using urinary cpDNA.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 6","pages":"Article 104124"},"PeriodicalIF":5.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567575","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":"74 Sarcomas Associated with Hemosiderotic Fibrolipomatous Tumor (HFLT): A Series of 16 Cases Detailing Clinical and Pathologic Features","authors":"Alexander Perez ,&nbsp;Jeanne Meis","doi":"10.1016/j.labinv.2024.102297","DOIUrl":"10.1016/j.labinv.2024.102297","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102297"},"PeriodicalIF":5.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678898","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":"76 Transverse Carpal Ligament Congo Red Evaluation as Screening Tool for Risk of Cardiac Amyloidosis","authors":"Maria Picken","doi":"10.1016/j.labinv.2024.102299","DOIUrl":"10.1016/j.labinv.2024.102299","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102299"},"PeriodicalIF":5.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678899","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":"51 GLI1-Altered Tumors share DNA Methylation Signature Irrespective of Anatomic Site, Morphology, or Molecular Alterations","authors":"Haya Homsi ,&nbsp;Jennifer Starbuck ,&nbsp;Joy Nakitandwe ,&nbsp;Riyam Zreik ,&nbsp;Akeesha Shah ,&nbsp;Reza Alaghehbandan ,&nbsp;Brian Rubin ,&nbsp;John Goldblum ,&nbsp;Steven Billings ,&nbsp;Josephine Dermawan ,&nbsp;Karen Fritchie","doi":"10.1016/j.labinv.2024.102274","DOIUrl":"10.1016/j.labinv.2024.102274","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102274"},"PeriodicalIF":5.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679264","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":"52 Clinicopathologic and Radiologic Characterization of Osteoid Osteoma, Osteoblastoma and Aggressive Osteoblastoma: A Retrospective Analysis of 264 Cases","authors":"Elsayed Ibrahim ,&nbsp;Khaled Mohamed ,&nbsp;Mahyar Khazaeli ,&nbsp;Valerae Lewis ,&nbsp;Jeanne Meis ,&nbsp;John Madewell ,&nbsp;Bogdan Czerniak","doi":"10.1016/j.labinv.2024.102275","DOIUrl":"10.1016/j.labinv.2024.102275","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102275"},"PeriodicalIF":5.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679265","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":"21 Respiratory Tract Localization of SARS-CoV-2 RNA in an Autopsy Series","authors":"Carolina Segura ,&nbsp;Hope Chang ,&nbsp;Daoqi Gao ,&nbsp;Judith Aronson","doi":"10.1016/j.labinv.2024.102243","DOIUrl":"10.1016/j.labinv.2024.102243","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102243"},"PeriodicalIF":5.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679383","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}