Journal of Pathology Clinical Research最新文献

{"title":"Validation of fibroblast activation protein and α-smooth muscle actin as prognostic biomarkers in prostate cancer through AI-assisted image analysis of dual-marker IHC","authors":"Jenni Säilä,&nbsp;Timo-Pekka Lehto,&nbsp;Antti Rannikko,&nbsp;Olli Kallioniemi,&nbsp;Tuomas Mirtti,&nbsp;Teijo Pellinen","doi":"10.1002/2056-4538.70068","DOIUrl":"10.1002/2056-4538.70068","url":null,"abstract":"<p>Prostate cancer (PCa) lacks reliable and accurate tissue-based biomarkers to support prognostic stratification and clinical treatment decisions. Current diagnostic assessment, including Gleason grading, has limitations such as interobserver variability and insufficient granularity for disease aggressiveness. Fibroblast activation protein (FAP) and α-smooth muscle actin (αSMA) have emerged as putative stromal biomarkers, but their prognostic value in localised PCa has not been validated at scale. In this study, we developed a novel artificial intelligence (AI)-augmented image analysis pipeline tailored for dual-marker immunohistochemistry of FAP and αSMA, enabling automated, tissue compartment-specific quantification of biomarker expression. This deep learning model was trained and validated using digitised high-resolution whole-slide images of tissue microarrays from three prostatectomy cohorts, comprising 4,097 cores from 835 patients with comprehensive clinical follow-up data. The AI pipeline demonstrated high accuracy in detecting epithelial, stromal, and immune compartments, as well as in quantifying FAP and αSMA signals. We validated stromal FAP as a robust prognostic marker consistently associated with adverse clinical outcomes, including earlier biochemical recurrence, metastasis, and cancer-specific death. Epithelial FAP and stromal αSMA showed additional prognostic associations in selected analyses, particularly in MRI-visible tumours. Our findings reinforce the biological and clinical relevance of stromal FAP in the prostate tumour microenvironment. By enabling standardised and scalable biomarker quantification, our newly developed AI-assisted workflow advances the clinical utility of FAP and αSMA and demonstrates the power of integrating digital pathology with biomarker quantification. This study represents a critical step toward implementing stromal biomarkers in routine PCa diagnostics and underscores the potential of AI-enhanced histopathology in advancing precision oncology.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776082","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148078220","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":"Systemic and local decorin levels mirror the clinical course of pancreatic cancer","authors":"Maja Svensson,&nbsp;Sophie Lehn,&nbsp;Hedda Jacobsen,&nbsp;Sofie Olsson Hau,&nbsp;Göran Jönsson,&nbsp;Kristian Pietras,&nbsp;Karin Jirström","doi":"10.1002/2056-4538.70066","DOIUrl":"10.1002/2056-4538.70066","url":null,"abstract":"<p>Despite significant progress in oncology research, pancreatic cancer remains inherently difficult to treat, and the mechanisms underlying therapeutic resistance remain unresolved. Decorin (DCN), a member of the family of small leucine-rich proteoglycans, has emerged as a versatile actor in various malignant diseases. The aim of this study was to further explore the potential clinical significance of DCN in pancreatic cancer, both regarding its dynamics in serum during chemotherapy and its compartmental and cellular distribution in tumour tissue. To this end, repeated on-treatment levels of soluble DCN were measured using proximity extension assay in 124 patients enrolled in a prospective, observational clinical study, inviting patients diagnosed with pancreatic or other pancreatobiliary-type periampullary adenocarcinoma eligible for adjuvant (<i>n</i> = 30) or first-line palliative (<i>n</i> = 94) chemotherapy. Multiplexed immunofluorescence was applied to map DCN and the associated immune landscape in resected tumours. The results showed increasing levels of DCN in serum after initiation of chemotherapy in palliative, but not in adjuvant, patients. A higher rate of change of serum DCN was an independent adverse prognostic factor in both treatment settings. There was no significant association between systemic levels and local DCN expression. Varying expression of DCN was denoted in both tumour cells, immune cells and stroma, but the prognostic significance was mainly assigned to its expression in B cells. In particular, a higher percentage of DCN positive B cells, overall and in interaction with tumour cells, were independent predictors of shorter survival. In summary, this study is the first to demonstrate the potential clinical utility of on-treatment monitoring of systemic DCN in patients with pancreatic cancer. The findings also provide interesting leads for further research into how DCN may interact with the immune microenvironment to promote tumour development and the emergence of chemoresistance.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12702688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758055","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":"Epigenetic similarity between adenoid ameloblastoma and dentinogenic ghost cell tumour: DNA methylation analysis in odontogenic tumours","authors":"Kyu-Young Oh","doi":"10.1002/2056-4538.70065","DOIUrl":"10.1002/2056-4538.70065","url":null,"abstract":"<p>Although adenoid ameloblastoma (AA) has recently been included in the WHO classification as a separate tumour type, its clinical, histological, immunohistochemical, and molecular similarities to dentinogenic ghost cell tumour (DGCT) raise questions about the current classification system. The aim of this study was to investigate the epigenetic similarity between AA and DGCT. A total of 35 odontogenic tumours consisting of 6 types, including 3 AAs and 4 DGCTs, were collected for this study. DNA methylation analysis was performed using the Infinium MethylationEPIC v2.0 BeadChip. Unsupervised clustering analysis was performed using <i>t</i>-distributed stochastic neighbour embedding (<i>t</i>-SNE) and Uniform Manifold Approximation and Projection (UMAP). No differentially methylated regions were identified between AA and DGCT. Both <i>t</i>-SNE and UMAP plots demonstrated that AAs clustered together with DGCTs, clearly separated from the other types of odontogenic tumour. Within the AA and DGCT methylation class, no subclasses were identified by the presence of the so-called AA-like histology, characterised by cribriform architecture and duct-like structures. These findings suggest a clear epigenetic similarity between AA and DGCT, further supporting the notion that the two tumours represent a spectrum of the same entity and may be better classified on a molecular basis as ‘WNT pathway-altered odontogenic tumours’.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662481","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148064373","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097812","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097813","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":"A membranous nephropathy variant mimicking minimal change disease","authors":"Chuqi Pan,&nbsp;Silin Xiang,&nbsp;Mengya Jiang,&nbsp;Yuan Li,&nbsp;Biao Huang,&nbsp;Tian Ye,&nbsp;Yuanyuan Du,&nbsp;Xuanli Tang,&nbsp;Yuan Yuan","doi":"10.1002/2056-4538.70062","DOIUrl":"10.1002/2056-4538.70062","url":null,"abstract":"<p>This study characterizes a novel disease pattern of membranous nephropathy (MN) that exhibits overlapping clinicopathological features with minimal change disease (MCD), termed ‘MCD-like MN’. Patients with histologically confirmed MN showing sparse and segmental subepithelial electron-dense deposits (EDD) but clinically resembling MCD were enrolled, alongside age- and gender-matched classic MCD and MN controls. Clinicopathological parameters were compared across groups. MN-associated antigens and MCD-related podocyte antigens were analyzed in renal tissues and serum. Among 107 archival MCD cases re-evaluated, 16 were reclassified as MCD-like MN based on EDD presence. Pathologically, these cases demonstrated IgG deposition in podocytes (62.5%), significantly higher than classic MCD (6.2%), but lacked complement activation and showed milder interstitial fibrosis compared to MN. Clinically, MCD-like MN patients presented a shorter disease duration and higher complete remission rates compared to MN (<i>p</i> &lt; 0.01), resembling classical MCD. Additionally, they had lower serum creatinine levels than MCD patients (<i>p</i> &lt; 0.01), which were more similar to MN levels. Furthermore, MN-associated antigens were detected in MCD-like MN cases and some of the serum antibodies' levels were increased, suggesting shared pathogenesis with MN, albeit with distinct immune features. Besides, spectrometry counts of podocyte antigens were not increased, and serum anti-podocyte antibodies were either absent or not elevated compared to MCD patients, ruling out antibody-mediated podocytopathy. Collectively, MCD-like MN represents a distinct MN subtype with atypical MCD-like clinicopathological features, likely driven by a unique immune mechanism divergent from both classic MN and MCD.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/2056-4538.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626256","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097814","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099498","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}