Pathobiology最新文献

{"title":"ThinPrep® Whole-Slide Digital Images versus Conventional Microscopy in Negative for Intraepithelial Lesion or Malignancy, Atypical Squamous Cells of Undetermined Significance, and Low-Grade Squamous Intraepithelial Lesion Cervical Lesions: European Federation of Cytological Societies (EFCS) Study.","authors":"Ester Puntonen, Sara Bazzon, Massimo Bongiovanni, Rosario Granados, Ines Krivak Bolanca, Maria Nasioutziki, Maurizio Pinamonti, Danijela Vrdoljak-Mozetic, Arrigo Capitanio, Beatrix Cochand-Priollet, Ambrogio Fassina, Giovanni Negri, Laura Ventura, Ivana Kholová","doi":"10.1159/000550455","DOIUrl":"10.1159/000550455","url":null,"abstract":"<p><strong>Introduction: </strong>High inter- and intraobserver variability is acknowledged in negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), and low-grade squamous intraepithelial lesion (LSIL) diagnostic categories in cervical cytology. As digital cytology has emerged, whole-slide images (WSIs) have been compared to conventional light microscopy (LM) to evaluate its feasibility in routine practice.</p><p><strong>Methods: </strong>Six cytopathologists evaluated 20 liquid-based cervical samples diagnosed as ASC-US, LSIL, or NILM with known hrHPV status, both by conventional LM and WSI, equalling 240 evaluations. Interobserver agreement was measured using Fleiss's kappa, Kendall´s coefficient and interclass correlation (ICC).</p><p><strong>Results: </strong>Most of the samples (93.75%) were assigned to the same original range of categories: NILM 5 (25%), ASC-US 10 (50%), and LSIL 5 (25%). WSI versus LM interobserver agreement varied with Fleiss's kappa (0.324 versus 0.319), Kendall's W (0.670 versus 0.572), and ICC (0.585 versus 0.414). Interobserver agreement for the ASC-US category was higher in Kendall's W (0.435 for WSI versus 0.329 for LM) and in ICC (0.394 versus 0.118). Fleiss's kappa showed lower interobserver agreement for ASC-US in WSI than LM (0.000 versus 0.039).</p><p><strong>Conclusion: </strong>This study illustrated that despite overall better agreement in WSI, ASC-US results were less favourable in WSI than LM, according to Fleiss's kappa test, but not other tests.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-11"},"PeriodicalIF":2.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-Based Multiomic Exploratory Analysis of the Urokinase Plasminogen Activator/uPAR System and Matrix Metalloproteinases in Stroma AReactive Invasion Front Areas-Positive Gastrointestinal Cancers.","authors":"Nic G Reitsam, Bianca Grosser, Sebastian Dintner, Veselin Grozdanov, Florian Sommer, Christian Heyer, Matthias Schlesner, Jochen Hardt, Simon Franz, Gerhard Schenkirsch, Andreas Probst, Phillip Löhr, Johanna Waidhauser, Bruno Märkl","doi":"10.1159/000549919","DOIUrl":"10.1159/000549919","url":null,"abstract":"<p><strong>Introduction: </strong>We recently proposed SARIFA (Stroma AReactive Invasion Front Areas), defined as direct tumour-adipocyte interaction, as an H&E-based histopathologic biomarker in gastrointestinal cancers, particularly gastric cancer (GC) and colorectal cancer (CRC). Despite SARIFA's well-validated prognostic value, its mechanistic underpinnings remain unclear. We hypothesized that extracellular matrix remodelling, specifically the plasmin/plasminogen activator system, may contribute to SARIFA formation.</p><p><strong>Methods: </strong>To test this, we compared the prognostic value of H&E-based SARIFA status with enzyme-linked immunosorbent assay (ELISA)-based protein levels of the serine proteases urokinase-type plasminogen activator (uPA, encoded by PLAU) and plasminogen activator inhibitor-1 (PAI-1, encoded by SERPINE1) in CRC. We further examined associations between SARIFA status and the plasmin/plasminogen activator system as well as downstream metalloproteinases using both protein (ELISA, immunohistochemistry) and bulk gene expression data (TCGA-COAD/READ and TCGA-STAD), as well as spatial gene expression profiling in CRC (n = 8) and GC (n = 12).</p><p><strong>Results: </strong>Our findings show that high expression of the plasmin/plasminogen activator system and downstream metalloproteinases correlates with SARIFA positivity. Digital spatial profiling revealed PLAU upregulation in tumour cells and PLAUR (encoding uPAR) upregulation in adjacent stromal cells at SARIFAs, suggesting a potential receptor-ligand interaction. Notably, SARIFA-positive tumours showed significantly higher numbers of tumour buds.</p><p><strong>Conclusion: </strong>These results provide new insights into the biological basis of SARIFAs and suggest therapeutic vulnerabilities related to the plasmin/plasminogen activator system.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-12"},"PeriodicalIF":2.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REV7 Expression Is Associated with Tumor Cell Growth and Cisplatin Resistance in Gallbladder Adenocarcinoma.","authors":"Masahiro Matsushita, Takuya Kato, Yasutaka Sakurai, Masaaki Ichinoe, Taro Kogami, Akihiro Tamaki, Yurika Kesen, Shoko Hayashi, Itaru Sanoyama, Yoshiko Numata, Atsuko Umezawa, Masatoshi Ichihara, Chika Kusano, Yoshiki Murakumo","doi":"10.1159/000549588","DOIUrl":"10.1159/000549588","url":null,"abstract":"<p><strong>Introduction: </strong>REV7 functions in various biological processes, including the DNA damage response. REV7 expression has been linked to the prognosis and chemoresistance in several human cancers. This study investigated the significance of REV7 in gallbladder adenocarcinoma (GBAC).</p><p><strong>Methods: </strong>REV7 expression was examined immunohistochemically in 77 resected GBAC specimens, and its association with clinicopathological features was analyzed. REV7-depleted GBAC cell lines were established, and the biological effects of REV7 depletion were evaluated.</p><p><strong>Results: </strong>High REV7 expression in GBAC tissues correlated with increased cell proliferation, as assessed by Ki-67 labeling indices (p < 0.001), and was associated with a trend toward shorter overall survival (p = 0.070) and significantly shorter post-progression survival (p = 0.035). REV7-knockout and REV7-knockdown cell lines derived from NOZ and G415 GBAC cells (NOZ-KO and G415-KD, respectively) showed reduced proliferation and increased sensitivity to cisplatin; however, REV7 depletion did not affect cell migration and invasion. Reintroduction of REV7 into NOZ-KO cells restores chemoresistance. Furthermore, RNA sequencing analysis comparing wild-type NOZ and NOZ-KOs revealed that REV7 inactivation downregulates genes involved in the DNA damage response.</p><p><strong>Conclusion: </strong>REV7 may contribute to tumor progression and chemoresistance in GBAC and may serve as a prognostic biomarker and molecular target for GBAC management.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-13"},"PeriodicalIF":2.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145945494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Histopathological Markers for Upstaging to Invasive Carcinoma after a Biopsy Diagnosis of Ductal Carcinoma in situ of the Breast: A Hypothesis-Generating Systematic Review.","authors":"Julia A M Riggi, Ibrahim Kassem, Christine Galant, Carolien H M van Deurzen, Martine Berlière, Mieke R Van Bockstal","doi":"10.1159/000547335","DOIUrl":"10.1159/000547335","url":null,"abstract":"<p><strong>Introduction: </strong>Around 25% of patients with a biopsy diagnosis of pure ductal carcinoma in situ (DCIS) will be upstaged to invasive breast carcinoma (IBC) after surgery. Because of this upstaging risk, patients with high grade DCIS frequently undergo a sentinel lymph node procedure (SLNP), which can cause surgery-induced morbidity. Presentation with a palpable mass increases the upstaging risk, but histopathological predictors are currently unclear. This PROSPERO-registered systematic review aims to identify which biopsy-based histopathological markers can predict the presence of IBC in the subsequent resection. These results might help to reserve SLNPs for selected high-risk patients, aiming to personalize treatment.</p><p><strong>Methods: </strong>PubMed, Embase, and Scopus were searched for content using predefined search queries. Three reviewers independently screened the literature in Rayyan by applying predefined criteria and retained 36 reports. Studies including DCIS with micro-invasion were excluded.</p><p><strong>Results: </strong>This systematic review comprised 18,475 patients. The median cohort size was 267 patients (range: 67-3,780). Most studies were retrospective (33/36). The median upstaging risk was 26% (range: 8-52%). The reports studied twenty-three histopathological and immunohistochemical features. Only seven features were investigated in multiple studies, all yielding contradictory results. For instance, thirty-three studies investigated nuclear grade, but only 18 reports demonstrated a significant association with upstaging, independent from cohort size.</p><p><strong>Conclusion: </strong>No robust histopathological features can be recommended at present to reliably predict the upstaging risk to IBC after a biopsy diagnosis of pure DCIS. We discuss several hypotheses, aiming to explain these contradictory data. Ideally, large-scale multicentre prospective studies should be organized to answer this unmet clinical need.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"34-47"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HPV ctDNA as a Biomarker for Monitoring Disease Progression in HPV16/18-Associated Cervical Cancer.","authors":"Meejeong Kim, Miseon Lee, Jun Kang, Sung Jong Lee, Sook Hee Hong, Keun Ho Lee, Ahwon Lee","doi":"10.1159/000548452","DOIUrl":"10.1159/000548452","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer, primarily driven by oncogenic HPV16/18, often relapses despite standard treatments. HPV circulating tumor DNA (ctDNA), which reflects tumor-derived genetic material in the bloodstream, has emerged as a promising noninvasive biomarker for monitoring disease progression.</p><p><strong>Methods: </strong>A prospective study was conducted on 20 patients with HPV16/18-associated cervical cancer. Posttreatment blood samples were collected, and HPV ctDNA levels were measured using droplet digital PCR. The correlation between HPV ctDNA levels and disease progression was examined.</p><p><strong>Results: </strong>HPV ctDNA was detected in 21% (18/85) of samples, with 6% (5/85) showing positivity. Patients without disease progression (n = 15) were HPV ctDNA negative, indicating a false positivity rate of zero. HPV ctDNA concentrations appeared higher in samples collected before or during disease progression, suggesting a potential association with disease status. Patients with positive HPV ctDNA tended to have shorter progression-free survival compared to those with negative ctDNA.</p><p><strong>Conclusions: </strong>This study suggests that HPV ctDNA may aid in monitoring disease progression in patients with HPV16/18-associated cervical cancer, highlighting the need for further validation.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"87-95"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma.","authors":"Hiroki Takase, Takao Fujisawa, Ryuichi Hayashi, Hideki Makinoshima, Yutaka Suzuki, Tomoyoshi Soga, Satoshi Fujii","doi":"10.1159/000548128","DOIUrl":"10.1159/000548128","url":null,"abstract":"<p><p><p>Introduction: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC).</p><p><strong>Methods: </strong>Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis/mass spectrometry on tumor and non-tumor tissues of the hypopharynx. Twenty-two patients who received adjuvant therapy after surgery were included. The receiver operating characteristic (ROC) and univariate and multivariate analyses were used to explore the relationship between recurrence-free survival (RFS), clinicopathological factors, and differentiated metabolites.</p><p><strong>Results: </strong>ROC analysis revealed six metabolites significantly associated with RFS in both cohorts, and multivariate analysis indicated that 2,3-pyridinedicarboxylate was a significantly independent poorer prognostic factor in the cohorts including patients with HPSCC without any adjuvant therapies (p = 0.017).</p><p><strong>Conclusion: </strong>2,3-Pyridinedicarboxylate, involved in NAD+ metabolism and genomic stability, suggests the possibility of developing molecular-targeted drugs for the production of metabolites related to prognosis. This study identifies novel prognostic metabolites and their associated metabolic pathways in HPSCC, highlighting potential therapeutic targets for treatment. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"72-86"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Tumourigenesis Mechanisms of Oncocytic Cell Tumours: Discoveries from a Comparative Omics Study.","authors":"Sule Canberk, Marta Ferreira, Arnaud Da Cruz Paula, Luísa Pereira, Carla Oliveira, Hugo Osório, Paula Soares, Valdemar Máximo","doi":"10.1159/000548985","DOIUrl":"10.1159/000548985","url":null,"abstract":"<p><strong>Introduction: </strong>Oncocytic cell tumours (OCTs), previously referred to as Hürthle cell tumours of the thyroid, are a subset of thyroid and endocrine neoplasms that pose diagnostic and therapeutic challenges owing to their unpredictable clinical behaviour. The transcriptomic and proteomic landscapes of OCTs remain poorly characterized compared with those of mitochondrion-rich neoplasms (MRNs: thyroid tumours with ≥75% oncocytic cells that share similar morphology but harbour nuclear driver mutations consistent with their respective histotypes rather than mitochondrial alterations).</p><p><strong>Methods: </strong>We performed RNA and protein sequencing on 12 OCT samples and 6 MRNs. This study was prompted by the understanding that oncocytic morphology alone does not necessarily predict tumour behaviour.</p><p><strong>Results: </strong>RNA sequencing analysis identified 47 downregulated and 38 upregulated differentially expressed genes (DEGs) in OCTs relative to MRNs, with significant enrichment in pathways related to heme metabolism. Protein sequencing further revealed 20 under-expressed and 64 over-expressed differentially expressed proteins (DEPs) in OCTs. Notably, all oncocytic carcinomas formed a distinct cluster separate from the MRNs, indicating a unique proteomic profile.</p><p><strong>Conclusion: </strong>Most of the DEPs were involved in three key cellular pathways: epigenetic regulation, the tumour microenvironment, and protein biogenesis, suggesting that these processes may underlie the distinctive morphology and behaviour of OCTs. These findings highlight the need for continued research into these molecular mechanisms to improve the diagnostic accuracy and develop targeted therapies for patients with OCTs.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"109-122"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Far Upstream Element-Binding Protein in Gastrointestinal Stromal Tumors and Its Regulation of Cell Proliferation, Migration, and Invasion.","authors":"Zhigao Zhang, Fucheng Zhang, Shubao Zhang, Xiaoling Song, Yonghong Xu, Yaojun Wang","doi":"10.1159/000547278","DOIUrl":"10.1159/000547278","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to observe the expression of far upstream element-binding protein 1 (FUBP1) in gastrointestinal stromal tumors (GISTs) and explore its impact on the biological behavior of GIST cells.</p><p><strong>Methods: </strong>Fifty patients with GIST who underwent surgical resection were selected, and cancer tissues and adjacent normal tissues were gathered. The expression level of FUBP1 and its correlation with clinicopathological data and prognosis in patients with GISTs were assessed. GIST-T1 cell lines in the logarithmic growth phase were transfected with lentiviruses overexpressing FUBP1, small hairpin RNA targeting FUBP1, and their respective negative controls. FUBP1 expression levels in each group, cell biological behavior were tested, and the effect of FUBP1 on tumor growth in vivo were tested.</p><p><strong>Results: </strong>Compared to adjacent normal tissues, FUBP1 expression level was elevated in GIST cancer tissues and was concerned with tumor size, NIH risk category, and tumor metastasis in patients. Knockdown of FUBP1 inhibited cell malignant behaviors and promoted cell apoptosis, while overexpression of FUBP1 had the opposite effects. FUBP1 facilitated the growth of GIST cells in vivo.</p><p><strong>Conclusion: </strong>FUBP1 is upregulated in GISTs and facilitates the invasion, migration, and proliferation of GIST cells. This provides a new perspective for understanding the pathogenesis of GIST and lays a foundation for developing potential therapeutic strategies targeting FUBP1.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"23-33"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Infiltration of Tissue-Resident Memory T Cells Predicts a Good Response to Anti-PD-L1 Immunotherapy in Extrahepatic Cholangiocarcinoma.","authors":"Yoshiyuki Tagayasu, Rin Yamada, Kosuke Kanemitsu, Yoshihiko Kondo, Yukio Fujiwara, Takumi Tanizaki, Rumi Itoyama, Yuki Kitano, Hiromitsu Hayashi, Yoshihiro Komohara, Masaaki Iwatsuki","doi":"10.1159/000547222","DOIUrl":"10.1159/000547222","url":null,"abstract":"<p><strong>Introduction: </strong>Extrahepatic cholangiocarcinoma (eCCA) is an aggressive malignancy with a poor prognosis. Immune checkpoint inhibitors (ICIs) targeting PD-L1 enhance antitumor immunity, but reliable predictive biomarkers remain unclear. This study investigated tumor-infiltrating immune cells, including T cells and macrophages, as potential biomarkers for ICI efficacy in eCCA.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 15 eCCA patients who received durvalumab for recurrent or unresectable disease after surgery. Immunohistochemical staining assessed PD-L1, HLA-class I/II, CD8, and CD103 expression in resected tumor specimens. ICI response was evaluated using RECIST 1.1 criteria and classified as partial response (PR), stable disease (SD), or progressive disease (PD). Correlations between immune cell infiltration and clinical outcomes were analyzed.</p><p><strong>Results: </strong>Five patients achieved PR, five SD, and five PD. CD8+ and CD103+ T-cell infiltration within tumor nests was significantly higher in PR and SD groups than in PD (p = 0.032, p = 0.0147). High HLA-class I expression correlated with response, while PD-L1 and HLA-class II showed no significant association. Patients with increased CD8+CD103+ T cells demonstrated better disease control.</p><p><strong>Conclusion: </strong>Intratumoral CD8+ and CD103+ T cells may serve as predictive biomarkers for ICI efficacy in eCCA, highlighting tissue-resident immune cells as therapeutic targets.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-11"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of ENPP1 in Testicular Germ Cell Tumors: Exploring Its Role in the Pathobiology of Distinct Histotypes and in Prognosis.","authors":"Miguel Bernardo Alves, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Alexandra Lapa, Rita Guimarães, Paula Lopes, Isaac Braga, Joaquina Maurício, Carmen Jerónimo, Rui Henrique, João Lobo","doi":"10.1159/000547655","DOIUrl":"10.1159/000547655","url":null,"abstract":"<p><strong>Introduction: </strong>Testicular germ cell tumors (TGCTs) are the most common solid malignancies among young men. Despite good response to cisplatin-based chemotherapy, side effects negatively affect quality of life. Recent development of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors opens opportunity for targeted therapy, but ENPP1 expression in TGCTs has not been characterized. We aimed to assess ENPP1 immunoexpression in a cohort of primary and metastatic TGCTs, and in normal testicular parenchyma, looking into differential immunoexpression patterns among subtypes and clinicopathological correlations.</p><p><strong>Methods: </strong>Overall, 90 TGCT individual tumor components from 63 patients diagnosed and treated at a comprehensive cancer center were assessed, using immunohistochemistry to ascertain biomarker expression (combined score of stained tumor cells percentage and intensity). In silico analysis of The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) datasets was performed for additional validation.</p><p><strong>Results: </strong>Significant differences in ENPP1 expression across TGCT subtypes were disclosed. Seminomas and embryonal carcinomas (ECs) showed significantly higher ENPP1 expression compared to other subtypes, the highest levels being found in EC, which was confirmed with in silico analysis of TCGA and HPA. Expression in metastatic samples was overall lower compared to primary TGCTs. ENPP1 was not expressed in germ cells of healthy testicular parenchyma.</p><p><strong>Conclusion: </strong>We demonstrate that ENPP1 is expressed in TGCTs, mostly EC (a frequently aggressive tumor subtype), followed by seminoma (the most common TGCT subtype), suggesting potential responsiveness to novel ENPP1 inhibitors. Absent expression in germ cells of healthy testicular parenchyma suggest cancer cells specificity and low probability of fertility-related toxicity.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"12-22"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}