Laboratory Investigation最新文献

{"title":"Detection and recurrence risk stratification of gastric cancer through DNA methylation profiling of blood.","authors":"Jing Guo, Shun Zhang, Shuang Zhou, Hui Wang, Kehui Xie, Chengcheng Ma, Zhixi Su, Rui Liu, Haiyan Han, Yiqin Pan, Jin Tong, Zhiguo Xiong, Liang Cheng, Renquan Lu, Xiaohua Jiang, Dazhi Xu","doi":"10.1016/j.labinv.2026.106132","DOIUrl":"https://doi.org/10.1016/j.labinv.2026.106132","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a blood-based DNA methylation assay for noninvasive detection of gastric cancer (GC) across all stages, including early and premalignant lesions, and to evaluate whether preoperative GasAiQ positivity is associated with postoperative recurrence risk in patients with resectable GC.</p><p><strong>Materials and methods: </strong>We used reduced representation bisulfite sequencing (RRBS) to profile DNA methylation patterns and identify tumor-specific differentially methylated regions (DMRs) between patients with GC and controls. The 24 most discriminatory DMRs were validated in an independent set of tissues and plasma and then incorporated into a quantitative methylation-specific PCR assay, GasAiQ. GasAiQ was evaluated in 1,372 individuals, including GC patients and those with gastritis, atrophy, intestinal metaplasia, or intraepithelial neoplasia, across three cohorts: training (n=518), validation (n=519), and independent test (n=335). Its association with recurrence risk was also assessed in 203 GC patients with resectable tumors for whom follow-up data were available after surgical resection.</p><p><strong>Results: </strong>GasAiQ demonstrated high diagnostic accuracy across all cohorts. In the training cohort, an area under the curve (AUC) of 0.904 was achieved, with 83.8% sensitivity, 82.6% specificity, and 83.2% accuracy. The performance remained robust in the validation (AUC 0.878, 83.9% sensitivity, 81.9% specificity, and 81.5% accuracy) and independent test (AUC 0.891, 83.5% sensitivity, 86.3% specificity, and 85.3% accuracy) cohorts. The detection rates for early-stage GC (stage I) ranged from 70.2% to 75.0%, and GasAiQ identified 57.6% high-grade intraepithelial neoplasia. Notably, in a multivariate Cox regression model adjusting for key clinicopathological factors, preoperative GasAiQ positivity remained significantly associated with recurrence risk (hazard ratio 7.5; 95% CI: 1.0-55.2; p = 0.047), supporting its potential prognostic value.</p><p><strong>Conclusions: </strong>GasAiQ is a noninvasive methylation assay that accurately detects gastric cancer, including early and premalignant stages, and predicts recurrence risk, offering significant potential for advanced screening, early diagnosis, and postoperative management.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"106132"},"PeriodicalIF":4.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839767","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":"ARHGEF26 Maintains SOX2 Stability by Inhibiting Ubiquitination to Enhance Glioblastoma Stemness","authors":"Xiao-Qing Chen ,&nbsp;Zhong-Yi Qin ,&nbsp;Zheng-Bo Li ,&nbsp;Jia-Feng Huang ,&nbsp;Na-Na Hou ,&nbsp;Wen-Juan Fu ,&nbsp;Qin Niu ,&nbsp;Shuai Wang ,&nbsp;Min Luo ,&nbsp;Cai-Die Tang ,&nbsp;Ying Guo ,&nbsp;Chang Liu ,&nbsp;Xiu-Wu Bian ,&nbsp;Zhuang Li ,&nbsp;Xiao-Hong Yao","doi":"10.1016/j.labinv.2026.106123","DOIUrl":"10.1016/j.labinv.2026.106123","url":null,"abstract":"<div><h3>Purpose</h3><div>Cancer stem cells represent a critical cell population that drives the malignant proliferation and invasiveness of glioblastoma (GBM), contributing to its poor prognosis. However, the mechanisms underlying the maintenance of stemness in GBM are poorly understood. This study aimed to investigate the role of Rho guanine nucleotide exchange factor 26 (ARHGEF26) in regulating GBM stemness and its underlying mechanism.</div></div><div><h3>Materials and Methods</h3><div>Human GBM specimens and non-tumor brain tissues were collected with ethical approval. GBM cell lines, and GBM stem cells (enriched by CD133+/CD15+ sorting) were cultured. We identified Rho guanine nucleotide exchange factor 26 (ARHGEF26) as a protein highly enriched in GBM stem cells and GBM tissues. Clinical correlation analysis was performed to assess the association between ARHGEF26 expression and patient survival. Gain-of-function and loss-of-function experiments were used to evaluate the effects of ARHGEF26 on GBM cell self-renewal, invasion, and tumorigenesis both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays were conducted to explore the molecular mechanism of ARHGEF26 in regulating GBM stemness. Bioinformatics analyses used data from TCGA, CGGA, Ivy Glioblastoma Atlas Project, and GlioVis. Experiments were repeated three times with GraphPad Prism-based statistical analyses.</div></div><div><h3>Results</h3><div>ARHGEF26 was significantly enriched in GBM stem cells and GBM tissues, and its high expression correlated with shorter overall survival in GBM patients. ARHGEF26 overexpression enhanced the self-renewal, invasion, and tumorigenesis of GBM cells both in vitro and in vivo. Mechanistically, ARHGEF26 interacted with and stabilized the core stemness transcription factor SOX2 by reducing its K48-linked polyubiquitination and subsequent proteasomal degradation.</div></div><div><h3>Conclusions</h3><div>Our findings reveal a novel role and mechanism for ARHGEF26 in promoting GBM stemness and suggest its potential as a therapeutic target.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"106 5","pages":"Article 106123"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623243","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":"Recommendations for Pathologist-led Deployment of Artificial Intelligence Tools as Lab-developed Tests.","authors":"Allen W Zhang, Matthew J Cecchini, Ali Bashashati, C Blake Gilks, Mary Kinloch, David F Schaeffer","doi":"10.1016/j.labinv.2026.106131","DOIUrl":"https://doi.org/10.1016/j.labinv.2026.106131","url":null,"abstract":"","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"106131"},"PeriodicalIF":4.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816336","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":"Upping the 'plex': Whole-slide, automated fourteen-color multiplex immunofluorescence staining of the tumor microenvironment in paraffin embedded tissue.","authors":"Jonathan Lai, Kyle S Cavagnini, Marcus Smith, Kemi Katemboh, Joel C Sunshine, Janis M Taube, Logan L Engle","doi":"10.1016/j.labinv.2026.106130","DOIUrl":"https://doi.org/10.1016/j.labinv.2026.106130","url":null,"abstract":"<p><strong>Purpose: </strong>Multiplex immunofluorescence (mIF) enables simultaneous visualization of multiple markers on a single slide. High-plex assays (>30 markers) typically rely on oligonucleotide (oligo)-tagged antibodies. Throughput of high-plex, oligo-based assays is limited, and results are not always comparable to gold-standard chromogenic immunohistochemistry (IHC), due to lack of amplification, particularly for immune checkpoint molecules such as PD-1 and PD-L1. In contrast, tyramide signal amplification (TSA)-based mIF improves detection sensitivity and throughput but is limited to fewer markers (5-8 markers). This study aimed to develop a combined oligo- and TSA-based mIF strategy to simultaneously detect 12-14 markers across whole-slide tissue sections, with equivalence to singleplex chromogenic immunohistochemistry (IHC) for each individual marker.</p><p><strong>Materials and methods: </strong>Various antibody stripping methods were evaluated, leading to optimization of a protocol using 2-mercaptoethanol/SDS/EDTA with heat to fully remove oligo-tagged antibodies. The finalized assay consisted of two phases. The first phase employed oligo-mIF to detect markers including CD3, CD4, CD8, CD68, PD-1, PD-L1, FoxP3, and a panCK/Sox10 cocktail, requiring two rounds of staining and imaging. Following complete removal of antibodies and fluorophores, a second phase using TSA-mIF was performed to detect LAG-3, Eomesodermin, T-bet, PD-1, PD-L1, and CD163.</p><p><strong>Results: </strong>The optimized stripping method successfully removed oligo-tagged antibodies, enabling sequential staining. Most oligo-mIF markers demonstrated comparable performance to gold-standard chromogenic IHC. However, PD-1 and PD-L1 did not achieve equivalency without amplification and only matched IHC performance when detected using TSA.</p><p><strong>Conclusions: </strong>A combined oligo- and TSA-based mIF assay was successfully developed, enabling detection of up to 12 markers with performance comparable to IHC. TSA remains necessary for detecting low-mid level PD-1 and PD-L1 expression. Future optimization will retain PD-1 and PD-L1 in the TSA phase and replace their oligo-based counterparts with non-amplification-dependent markers, expanding the assay to 14 markers and enhancing whole-slide characterization of the tumor microenvironment.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"106130"},"PeriodicalIF":4.2,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816422","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":"Impact of Copy-number Alterations on Human Papillomavirus (HPV)-Induced and HPV-Independent Penile Cancers.","authors":"Mikhail S Ermakov, Sigrid Regauer, Karl Kashofer","doi":"10.1016/j.labinv.2026.106129","DOIUrl":"https://doi.org/10.1016/j.labinv.2026.106129","url":null,"abstract":"<p><p>Penile squamous cell carcinomas (SCC) develop via a transforming human papillomavirus (HPV) infection or independent of HPV. We assessed the role of copy-number alterations (CNA) affecting chromosome arms, oncogenes and tumor suppressor genes (TSG) in 121 penile SCC (52% HPV-associated and 48% HPV-independent) using shallow whole-genome sequencing. CNA were common and complex, with frequent co-occurrences. Neither etiology had exclusive CNA. Arm-level changes included gains of 3q and 8q (48% each), 1q (36%), 1p (26%), 9q (36%) and 9p (31%) and losses of 19p (48%), 8p (44%), 1q (36%), and 3p (33%) of SCC. Oncogene amplifications included broad 3q alterations affecting TP63, SOX2, PIK3CA (43%) and 8q including MYC, HEY, RAD21 (40%). Homozygous deletions affected WRN, NRG1 (8p;29%), BAP1, FANCD2, VHL (3p) and ARHGEF12, BCL9L, ATM (11q22/23) in 19% each. CNA affecting TP53, CDKN2A/B, CDKN1A/B, and RB1 occurred in similar numbers in HPV-induced (16%) and HPV-independent SCC (24%) quite in contrast to TSG somatic mutations exclusive to HPV-independent SCC associated with lichenoid dermatoses. HPV-induced SCC had more 1p amplifications (adj. p=.003), while HPV-independent SCC carried more 8q full-arm gains (adj. p=.00003), amplifications of oncogenes on 8q (adj. p=.006) including MYC and homozygous deletions of 8p (adj. p=.03). MYC amplifications coincided with an increased fraction of genome altered indicative for genomic instability (p=.00001). EGFR amplifications dominated in HPV-negative wild-type TP53/CDKN2A SCC without dermatoses. Together with mutations in PIK3CA, HRAS and FGFR3 they represent an alternative RTK/Ras/PI3K-mediated carcinogenesis pathway. More than half of advanced SCC irrespective of etiology harbored targetable CNA such as EGFR, MTAP, ATM.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"106129"},"PeriodicalIF":4.2,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775458","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":"KLK10 Upregulation Drives Aggressiveness and Radioresistance and Has a Negative Prognostic Impact on Rectal Cancer.","authors":"Chia-Lin Chou, Cheng-Wei Lin, Wan-Shan Li, Sung-Wei Lee, Yu-Hsuan Kuo, Yow-Ling Shiue, Chien-Feng Li, Hong-Yue Lai, Ching-Chieh Yang","doi":"10.1016/j.labinv.2026.106128","DOIUrl":"https://doi.org/10.1016/j.labinv.2026.106128","url":null,"abstract":"<p><p>Rectal cancer is a heterogeneous disease with widely variable treatment responses. Beyond the tumor-node-metastasis (TNM) staging system, no reliable biomarkers currently exist to predict the efficacy of concurrent chemoradiotherapy (CCRT) in rectal cancer, limiting the personalization of curative-intent treatment. Proteolytic enzymes promote extracellular matrix degradation and tumor progression, with serine proteases playing a key role. Consequently, this study intended to investigate their potential to predict preoperative CCRT response and survival in rectal cancer. In our rectal cancer cohort (n = 343), high kallikrein-related peptidase 10 (KLK10) immunoreactivity was considerably linked to adverse clinicopathologic characteristics, comprising pre-CCRT nodal status (cN1-2; p = 0.032), post-CCRT tumor stage (ypT3-4; p = 0.001), post-CCRT nodal status (ypN1-2; p < 0.001), perineural invasion (p < 0.001), vascular invasion (p < 0.001), and poor tumor regression (p = 0.001). Multivariate survival analyses indicated that high KLK10 immunoreactivity was independently correlated with worse disease-specific survival [hazard ratio (HR), 3.647; 95% confidence interval (CI), 1.854-7.171; p < 0.001], locoregional recurrence-free survival (HR, 3.591; 95% CI, 1.523-8.463; p = 0.003), and metastasis-free survival (HR, 2.459; 95% CI, 1.346-4.492; p = 0.003). Additionally, cellular analyses revealed that KLK10 contributes to cancer progression by promoting aggressive phenotypes and radiation resistance. These findings suggest that KLK10 could be a predictive and prognostic biomarker as well as a promising therapeutic target in rectal cancer.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"106128"},"PeriodicalIF":4.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775541","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":"Scoring Reliability of c-Met Immunohistochemical Assays in Lung Adenocarcinoma","authors":"Yang Zhou ,&nbsp;Junyi Pang ,&nbsp;Yumeng Cai ,&nbsp;Longyun Chen ,&nbsp;Yinbo Xiao ,&nbsp;Yining Zhen ,&nbsp;Xianlong Chen ,&nbsp;Zhiyong Liang ,&nbsp;Xiaohua Shi","doi":"10.1016/j.labinv.2026.106078","DOIUrl":"10.1016/j.labinv.2026.106078","url":null,"abstract":"<div><div>c-Met overexpression may identify patients who benefit from MET inhibitor therapy. However, concordance among c-Met immunohistochemistry (IHC) assays and scoring system reliability remain unclear. We retrospectively analyzed 150 lung adenocarcinoma specimens (from December 2018 to March 2023) using 5 c-Met IHC assays (SP44_R, SP44_Z, D1C2, LBP4-C-MET, and 811B7F4), scored by H-score, clinical score, 2-tier H-score (H-score ≥150 as positive) and 2-tier clinical score (clinical score 2+/3+ as positive). Next-generation sequencing for <em>MET</em> alterations was performed on 107 samples. H-scores of the 5 assays showed excellent interassay reliability (intraclass correlation coefficient = 0.953). Compared with SP44_R, which is the most frequently used antibody in the clinical trial, SP44_Z had the highest correlation with it (ρ = 0.851), followed by D1C2 (ρ = 0.818), LBP4-C-MET (ρ = 0.786), and 811B7F4 (ρ = 0.737). Among the 5 assays, Kendall <span><math><mrow><mi>W</mi></mrow></math></span> for the clinical score was 0.697; Fleiss κ for the 2-tier H-score was 0.51 and for the 2-tier clinical score was 0.494. In comparison with the clinical score 3+ of SP44_R, SP44_Z and 811B7F4 showed moderate reliability (κ = 0.483), LBP4-C-MET (κ = 0.459), and D1C2 (κ = 0.234). Nearly perfect agreement existed between the 2-tier H-score and clinical score (κ range: 0.944-0.986). In contrast, correlation analysis between H-scores across all assays and RNA expression levels revealed a weak association (ρ = 0.159-0.349). Five c-Met IHC assays demonstrated moderate-to-strong concordance in detecting c-Met overexpression. SP44_R, SP44_Z, LBP4-C-MET, and 811B7F4 performed reliably, although D1C2 was less consistent for clinical score 3+. A clinical score of 2+/3+ or an H-score of ≥150 is associated with high diagnostic consistency, supporting multiple validated IHC assays for c-Met evaluation in lung adenocarcinoma.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"106 4","pages":"Article 106078"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131941","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":"General Pathologists Achieve Near-Specialist Diagnostic Performance Using Deep Learning–Based Virtual Staining for Donor Kidney Assessment: A Retrospective-Prospective Diagnostic Concordance Study","authors":"Jin-Peng Cen ,&nbsp;Sheng-Dong Ge ,&nbsp;Yang-Shu Zhou ,&nbsp;Yu-Zhu Li ,&nbsp;Ze-Feng Guo ,&nbsp;Rong Peng ,&nbsp;Yong-Guang Liu ,&nbsp;Song Zhou ,&nbsp;Shuo-Yu Xu ,&nbsp;Shan-Chao Zhao ,&nbsp;Ding Liu","doi":"10.1016/j.labinv.2026.106077","DOIUrl":"10.1016/j.labinv.2026.106077","url":null,"abstract":"<div><div>Conventional rapid evaluation of donor kidney quality primarily relies on hematoxylin and eosin (H&amp;E) staining, which inadequately visualizes collagen fibers, compromising the assessment of interstitial fibrosis and posing challenges for general pathologists (GPs) lacking specialized renal training. This study investigated whether artificial intelligence–based virtual staining could enhance donor kidney evaluation, particularly for interstitial fibrosis and chronic pathologies. Using 187 paired whole-slide images of H&amp;E and Masson’s trichrome–stained sections, we developed and validated a CycleGAN-based virtual staining model that transforms H&amp;E images into virtual Masson’s trichrome (VMT) representations. A renal pathologist (RP) and 2 GPs (GP.1 and GP.2) evaluated interstitial fibrosis and chronic changes using the Remuzzi scoring system, comparing results with and without virtual staining. Prospective validation was performed on 46 frozen sections. Results demonstrated that VMT effectively visualized interstitial collagen fibers, enabling more reliable fibrosis classification. Diagnostic accuracy significantly improved with virtual staining versus H&amp;E alone (weighted kappa: GPs improved from 0.39-0.51 to 0.78-0.82; RP from 0.61 to 0.86), and interobserver agreement markedly increased (GPs: 55%-64% to 84%-88%; RP: 71%-90%). Notably, VMT bridged the expertise gap, allowing GPs to achieve near-specialist performance in fibrosis assessment (weighted kappa: GP.1 from 0.48 to 0.82; GP.2 from 0.41 to 0.84). Prospective validation confirmed these advantages, showing superior accuracy when combining VMT with H&amp;E versus H&amp;E alone (weighted kappa: GP.1 from 0.27 to 0.65; GP.2 from 0.34 to 0.68). The technology also enhanced glomerulosclerosis detection (GPs’ kappa = 0.82-0.87) and transplant decision-making accuracy (kappa = 0.84-0.85), elevating GPs to specialist-level competence. In conclusion, deep learning–based virtual staining significantly improves the precision of donor kidney evaluations by GPs, approaching specialist-level performance. This technology offers an efficient, cost-effective solution for assessing fibrosis and chronic pathologies, potentially eliminating diagnostic disparities between GPs and specialist pathologists in transplantation medicine.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"106 4","pages":"Article 106077"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119404","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":"Diagnostic Potential of Tn-MUC1 in Breast Cancer: A Novel Immunohistochemical Marker Reflecting Tumor Progression","authors":"Ai Shimizu ,&nbsp;Kanako C. Hatanaka ,&nbsp;Ayae Nange ,&nbsp;Asami Okumura ,&nbsp;Masanori Takehashi ,&nbsp;Yoshiki Shinomiya ,&nbsp;Kentaro Naruchi ,&nbsp;Masaharu Sato ,&nbsp;Hiroshi Kase ,&nbsp;Tomoko Mitsuhashi ,&nbsp;Hiroko Yamashita ,&nbsp;Yutaka Hatanaka ,&nbsp;Yoshihiro Matsuno","doi":"10.1016/j.labinv.2025.106070","DOIUrl":"10.1016/j.labinv.2025.106070","url":null,"abstract":"<div><div>Mucin 1 (MUC1) is a highly O-glycosylated transmembrane glycoprotein. Tumor-associated MUC1, characterized by aberrant O-linked glycans, is overexpressed in cancer cells; however, conventional MUC1 antibodies show limited specificity for tumor-associated glycan structures. Recently, a novel epitope-defined antibody (MUC1-Tn antigen epitope-defined antibody [MUC1-Tn ED Ab]) that specifically recognizes the Tn-MUC1 antigen was developed. In this study, we evaluated the potential of MUC1-Tn ED Abs as diagnostic markers of breast cancer. Tissue microarray sections from 124 patients with invasive breast carcinoma (IBC) and 26 whole tissue sections, including multiple neoplastic lesions—flat epithelial atypia (n = 24), ductal carcinoma in situ (n = 26), and IBC (n = 16)—were analyzed. Immunohistochemical distributions of Tn-MUC1 and MUC1 were assessed using the MUC1-Tn ED Ab (clone SN102) and a conventional antibody (clone Ma552), respectively. In tissue microarray analysis, Tn-MUC1 exhibited minimal immunoreactivity in nonneoplastic areas and high specificity for IBC. In IBC tissues, immunoreactivity with Tn-MUC1 was predominantly cytoplasmic, unlike conventional MUC1 staining observed in both the cytoplasm and membrane. In multilesion analysis, cytoplasmic Tn-MUC1 expression was rarely detected in nonneoplastic areas but progressively increased across flat epithelial atypia, ductal carcinoma in situ, and IBC. Knockdown assays in breast cancer cell lines demonstrated that core 1 β1,3-galactosyltransferase 1 (C1GALT1), an enzyme involved in galactosylation of the Tn antigen, significantly influenced the cellular localization of Tn-MUC1. This study demonstrates that Tn-MUC1, as detected by the MUC1-Tn ED Ab, has high specificity for breast cancer and may act as a novel immunohistochemical marker reflecting tumor progression.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"106 3","pages":"Article 106070"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934348","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":"Differential Expression of P-Element–Induced Wimpy Testis (PIWI)–Interacting RNAs in Glioblastoma Stem Cells Affects Their Biological Features: Implications for Tumor Progression and Patient Survival","authors":"Frantisek Siegl ,&nbsp;Elena Garcia-Borja ,&nbsp;Rosana Mateu ,&nbsp;Karolina Trachtova ,&nbsp;Matej Jasik ,&nbsp;Martin Kopecky ,&nbsp;Marek Vecera ,&nbsp;Lenka Radova ,&nbsp;Michal Hendrych ,&nbsp;Tomas Kazda ,&nbsp;Pavel Fadrus ,&nbsp;Aleksi Sedo ,&nbsp;Ondrej Slaby ,&nbsp;Petr Busek ,&nbsp;Jiri Sana","doi":"10.1016/j.labinv.2026.106072","DOIUrl":"10.1016/j.labinv.2026.106072","url":null,"abstract":"<div><div>Glioblastoma isocitrate dehydrogenase–wild-type (GBM) is the most lethal and, concurrently, the most common malignant primary brain tumor. Its aggressive behavior is associated with the presence of a subpopulation of glioblastoma stem cells (GSCs) that drive resistance to therapy and early relapse. P-element–induced wimpy testis–interacting RNAs (piRNAs), which are characteristically expressed in undifferentiated cells, are thought to play an important role in GSC biology. To identify piRNAs associated with GSCs, we selected 24 paired GSC and non-GSC cultures from patients with GBM based on the expression of stem cell markers CD133 and Sox2, ability of GSCs to form spheres in culture, and to differentiate and replicate tumors in immunodeficient mice. Global piRNA profiling using next-generation sequencing revealed 98 significantly differentially expressed piRNAs in GSCs compared with non-GSCs, including piR-9491, whose dysregulation in GBM has been previously described. Downregulation of piR-9491 in GSCs led to decreased viability, growth, invasion, and increased apoptosis. Significance of piRNA pathway for GBM pathology was further highlighted by identification of 34 piRNAs connected to patients' survival. These molecules were further used for the establishment of a piRNA signature predicting survival of patients with GBM. Our results not only confirm the important role of piR-9491 in GSCs but also indicate a potential significant role of piRNAs in the biology of GBM.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"106 3","pages":"Article 106072"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989821","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}