Pathobiology最新文献

{"title":"Keratin 24 Predicts Poor Prognosis in Breast Cancer.","authors":"Emad Rakha, Yousif A Kariri, Mansour Alsaleem, Taher A Kariri, Mohammed Alkharaiji, Mohammed Asad, Emad A Rakha","doi":"10.1159/000546022","DOIUrl":"10.1159/000546022","url":null,"abstract":"<p><p><p>Introduction: Keratin (KRT) 24 is a cytoskeletal protein that plays a major role in the formation of intermediate filaments to provide mechanical stability. KRT24 overexpression facilitates tumour cell migration, invasion, and metastasis in several types of cancers. This study evaluates the clinicopathological significance of KRT24 expression in large breast cancer (BC) cohorts with long-term follow-up.</p><p><strong>Methods: </strong>KRT24 mRNA expression was assessed in publicly available BC datasets (n = 13,025). KRT24 protein expression was evaluated immunohistochemically using well-characterised operable BC cohort (n = 832), and associations with clinicopathological features and patients' outcomes were evaluated.</p><p><strong>Results: </strong>The KRT24 expression, at both transcriptomic and protein levels, was associated with features indicative of poor prognosis, including high histological grade, ER negativity, and HER2 positivity, and with poor patient outcomes. High KRT24 protein expression in chemotherapy-treated patients was significantly correlated with a shorter survival, a higher risk of distant metastases, and BC-related deaths. Additionally, patients with high KRT24 mRNA expression exhibited dysregulation of several differentially expressed genes and enriched pathways, including the cytokine-cytokine receptor interaction pathway, IL-17 signalling pathway, and oestrogen signalling pathway.</p><p><strong>Conclusion: </strong>KRT24 expression is associated with poor prognosis in BC. It also plays a predictive role in advanced BC and may represent a potential therapeutic target for patients with this aggressive disease. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"251-264"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975530","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":"Single-Cell Transcriptomic Analysis of Myeloid Lineage Evolution from CD19 CAR-T Cell Therapy.","authors":"Yajuan Cui, Peilong Wang, Hongkai Zhu, Zhihua Wang, Huifang Zhang, Haodong Xu, Ruijuan Li, Yue Sheng, Hongling Peng","doi":"10.1159/000544038","DOIUrl":"10.1159/000544038","url":null,"abstract":"<p><strong>Introduction: </strong>We report a case of relapse and refractory acute B-lymphoblastic leukemia (r/r B-ALL) apparently turned into acute myeloid leukemia, which is occasional and fatal during CAR-T treatment. There are still limited data to clarify the molecular mechanism of myeloid blast populations proliferation during CAR-T treatment.</p><p><strong>Case presentation: </strong>A 21-year-old man with an established history of r/r B-ALL with a complex chromosome karyotype and renal extramedullary infiltration presented to our institution. He exhibited a rapid relapse with acute monocytic leukemia 19 days after CD19 CAR-T cell infusion with extensive infiltration of skin and brain. Salvage chemotherapy was ineffective, and he subsequently succumbed to the uncontrolled invasion and infiltration of leukemia cells and hemorrhage. RNA velocity analysis predicted that HSCs differentiated into GMPs and then GMPs differentiated into myeloid lineage cells. The ANXA1-FPR1/2 axis expression was significantly increased post-treatment, which promotes tumor cell proliferation, invasion, and angiogenesis. 6q deletion (6q-) was the common genetic abnormality across all cell populations, indicating that 6q- conferred a survival ability to HSCs during CAR-T cell therapy.</p><p><strong>Conclusions: </strong>This case demonstrates potential mechanisms of clone evolution molecular events that CD19 CAR-T cell infusion accelerated the existing myeloid lineage evolution via ANXA1-FPR1/2 axis expression from HSCs with 6q-. (Cyto-)genetic aberrations and/or pathways previously not included in the risk stratification of B-ALL might well be predictive for response and outcome in the era of immunotherapy.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"180-186"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382859","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":"Erratum.","authors":"","doi":"10.1159/000543584","DOIUrl":"10.1159/000543584","url":null,"abstract":"","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"121-122"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597479","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":"Next-Generation Integrated Sequencing Identifies Poor Prognostic Factors in Patients with MYD88-Mutated Chronic Lymphocytic Leukemia in Taiwan.","authors":"Ying-Jung Huang, Jing Quan Lim, Jacob Shujui Hsu, Ming-Chung Kuo, Po-Nan Wang, Hsiao-Wen Kao, Jin-Hou Wu, Chiu-Chen Chen, Shih-Feng Tsai, Choon Kiat Ong, Lee-Yung Shih","doi":"10.1159/000541709","DOIUrl":"10.1159/000541709","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western countries and is very rare in Asia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 215 patients with CLL were analyzed by using next-generation sequencing to investigate the ethnic differences in genetic abnormalities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Whole-genome sequencing and whole-exome sequencing analyses on 30 cases showed that 9 genes, including IGLL5, MYD88, TCHH, DSCAM, AXDND1, BICRA, KMT2D, MYT1L, and RBM43, were more frequently mutated in our Taiwanese cohort compared with those of the Western cohorts. IGLL5, MYD88, and KMT2D genes were further analyzed by targeted sequencing in another 185 CLL patients, unraveling frequencies of 29.3%, 20.9%, and 15.0%, respectively. The most frequent positional mutation of MYD88 was V217F (26/45, 57.8%), followed by L265P (9/45, 20.0%). MYD88 mutations were significantly associated with IGLL5 mutations (p = 0.0004), mutated IGHV (p &lt; 0.0001) and 13q deletion (p = 0.0164). CLL patients with co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations were associated with a significantly inferior survival compared to those with MYD88 mutation alone (not reached vs. 131.8 months, p = 0.007). In multivariate analysis, MYD88 mutation without KMT2D or IGLL5 mutations was an independently favorable predictor.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western countries and is very rare in Asia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 215 patients with CLL were analyzed by using next-generation sequencing to investigate the ethnic differences in genetic abnormalities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Whole-genome sequencing and whole-exome sequencing analyses on 30 cases showed that 9 genes, including IGLL5, MYD88, TCHH, DSCAM, AXDND1, BICRA, KMT2D, MYT1L, and RBM43, were more frequently mutated in our Taiwanese cohort compared with those of the Western cohorts. IGLL5, MYD88, and KMT2D genes were further analyzed by targeted sequencing in another 185 CLL patients, unraveling frequencies of 29.3%, 20.9%, and 15.0%, respectively. The most frequent positional mutation of MYD88 was V217F (26/45, 57.8%), followed by L265P (9/45, 20.0%). MYD88 mutations were significantly associated with IGLL5 mutations (p = 0.0004), mutated IGHV (p &lt; 0.0001) and 13q deletion (p = 0.0164). CLL patients with co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations were associated with a significantly inferior survival compared to those with MYD88 mutation alone (not reached vs","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"77-89"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366117","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":"Duodenal Foveolar Adenoma: Case Presentation with Whole Exome Sequencing and Review of the Literature.","authors":"Ádám Ferenczi, Sofia Germano, Joana Afonso, Levente Kuthi, Tamás Lantos, Anita Sejben","doi":"10.1159/000546139","DOIUrl":"10.1159/000546139","url":null,"abstract":"<p><p><p>Introduction: Duodenal adenomas are most commonly associated with polyposis syndromes. Foveolar adenoma is an especially rare entity with an unknown aetiology. We present a case of duodenal foveolar adenoma with coexisting metaplasia, whole exome sequencing results, and the first literature review. Case Presentation: Hereby, we present the case of a 58-year-old man, whose polypectomy specimen revealed a lesion composed of mainly foveolar cells with low-grade dysplasia and was concluded as foveolar adenoma. Due to the incomplete resection, polypectomy was repeated; this time, foveolar adenoma was diagnosed with high-grade dysplasia. Foveolar differentiation was proved with MUC5AC immunohistochemistry; in addition, KRAS and SMAD4 pathogenic mutations were identified. Discussion: Duodenal foveolar adenoma remains a controversial and an enigmatic entity. Our paper presents such a lesion with first low-grade, then high-grade dysplasia, and KRAS mutation, identical to gastric manifestations. The further sample of our patient suggests foveolar metaplasia as an aetiological factor that supports the literature data. </p>.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"300-305"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174482","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":"Nodal T-Cell Lymphoma Transdifferentiated from Mantle Cell Lymphoma with Epstein-Barr Virus Infection.","authors":"Paul D Barone, Wayne Tam, Julia T Geyer, John P Leonard, Adrienne Phillips, Madhu M Ouseph","doi":"10.1159/000541974","DOIUrl":"10.1159/000541974","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;We report a case of mantle cell lymphoma (MCL) with an apparent lineage switch to an EBV-positive T-cell lymphoma. Although lineage switch is a well-documented phenomenon in some hematolymphoid diseases, such as acute leukemias or histiocytic/dendritic cell neoplasms, lineage switch from mature B-cell to T-cell lymphoma is exceedingly rare.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Case presentation: &lt;/strong&gt;A 55-year-old man with an established history of MCL presented to our institution. Peripheral blood flow cytometry was consistent with MCL. Biopsy of a lumbar vertebral fracture site demonstrated MCL, EBV-associated, with large cells reminiscent of high-grade transformation (BCL1-positive). Two months later, a lymph node biopsy demonstrated an EBV-positive T-cell lymphoma without phenotypic evidence of B-cell lymphoma (BCL1-negative). Cytogenetic testing revealed CCND1::IGH fusion in all three specimens. IGH/IGK clonality testing revealed conserved monoclonal peaks in all three samples; TCR clonality testing revealed monoclonal peaks in the T-cell lymphoma, only. NGS-based molecular genetic studies revealed shared mutations between the three samples, consistent with a clonal relationship suggesting evolution from MCL to T-cell lymphoma.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This case demonstrates that lineage switch from mature B-cell to mature T-cell phenotype is possible in certain settings. Whether lineage switch in this case was potentiated by EBV infection is unclear. The loss of BCL1 expression in the T-cell lymphoma, despite conservation of the CCND1::IGH fusion, may be attributable to the downregulation of the IGH promoter as part of the shift from B-cell to T-cell phenotype.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;We report a case of mantle cell lymphoma (MCL) with an apparent lineage switch to an EBV-positive T-cell lymphoma. Although lineage switch is a well-documented phenomenon in some hematolymphoid diseases, such as acute leukemias or histiocytic/dendritic cell neoplasms, lineage switch from mature B-cell to T-cell lymphoma is exceedingly rare.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Case presentation: &lt;/strong&gt;A 55-year-old man with an established history of MCL presented to our institution. Peripheral blood flow cytometry was consistent with MCL. Biopsy of a lumbar vertebral fracture site demonstrated MCL, EBV-associated, with large cells reminiscent of high-grade transformation (BCL1-positive). Two months later, a lymph node biopsy demonstrated an EBV-positive T-cell lymphoma without phenotypic evidence of B-cell lymphoma (BCL1-negative). Cytogenetic testing revealed CCND1::IGH fusion in all three specimens. IGH/IGK clonality testing revealed conserved monoclonal peaks in all three samples; TCR clonality testing revealed monoclonal peaks in the T-cell lymphoma, only. NGS-based molecular genetic studies revealed shared mutations between the three samples, consistent with a clonal relationship suggesting evolution from MCL to T-cell lymphoma.&lt;/p&gt;&lt;p&gt;&lt;","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"109-120"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471983","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":"Deciphering Breast Origin in Malignant Effusions: The Diagnostic Utility of an MGP, GATA-3, and TRPS-1 Immunocytochemical Panel.","authors":"So Hyeon Yang, Jae Seok Lee, Ji Won Koh, Ilias P Nikas, Eun Na Kim, Hyebin Lee, Han Suk Ryu","doi":"10.1159/000540989","DOIUrl":"10.1159/000540989","url":null,"abstract":"<p><strong>Introduction: </strong>Defining the origin of metastatic cancer is crucial for establishing an optimal treatment strategy, especially when obtaining sufficient tissue from secondary malignancies is limited. While cytological examination is often used in this diagnostic setting, morphologic analysis alone often fails to differentiate metastases derived from the breast from other primaries. The hormone receptor, human epidermal growth factor receptor-2, gross cystic disease fluid protein 15, and mammaglobin immunohistochemistry are often used to diagnose metastatic breast cancer. However, their effectiveness decreases in estrogen receptor (ER)-negative breast cancers, including the triple-negative breast cancer (TNBC) subtype.</p><p><strong>Methods: </strong>We conducted a comprehensive evaluation of GATA-binding protein 3 (GATA-3), trichorhinophalangeal syndrome type 1 (TRPS-1), and Matrix Gla Protein (MGP) immunochemistry across 140 effusion cytology specimens with metastatic adenocarcinoma derived from various primaries, including the breast, colon, pancreaticobiliary, lung, tubo-ovarian, and stomach.</p><p><strong>Results: </strong>The expression rates of these immunomarkers were significantly higher in metastatic cancers originating from the breast than other primaries. In TNBC, TRPS-1 (80.00%) and MGP (65.00%) exhibited higher positivity rates compared to GATA-3 (40.00%). Additionally, our data suggest that an immunohistochemical panel comprising MGP, GATA-3, and TRPS-1 significantly enhances the detection of metastatic breast cancer in effusion cytology specimens, including TNBC in particular. When considering dual-marker positivity, the diagnostic accuracy was found to be 89.29% across all breast cancer subtypes and 92.93% for TNBC.</p><p><strong>Conclusions: </strong>MGP appears to be a robust marker for identifying metastatic breast cancer in malignant effusions, especially TNBC. MGP notably enhances diagnostic accuracy when incorporated together with GATA-3 and TRPS-1 in an immunohistochemical panel.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"40-51"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081175","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":"Immuno-Activated, Highly Expressing PD-1 Phenotype in Hepatocellular Carcinoma Is Associated with a Lower Recurrence Rate.","authors":"Gabriel F Hess, Caner Ercan, Alexander Wilhelm, Jasmin Zeindler, Mairene Coto-Llerena, Silvio Däster, Simone Muenst, Jürg Vosbeck, Luca Di Tommaso, Martin Bolli, Luigi M Terracciano, Otto Kollmar, Salvatore Piscuoglio, Savas D Soysal","doi":"10.1159/000543933","DOIUrl":"10.1159/000543933","url":null,"abstract":"<p><strong>Introduction: </strong>Curative treatments in early-stage hepatocellular carcinoma (HCC) are limited by high recurrence rates, and targeted therapies against HCC are rare. Tumour microenvironment (TME) plays a crucial role. One strategy is the expression of programmed cell death receptor 1 ligand (PD-L1), whose receptor PD-1 is expressed on activated T cells. The use of immune checkpoint inhibitors (ICIs) has shown antitumour activity. In HCC, ICIs are proposed as a possible first- and second-line therapy. The expression of PD-1 and PD-L1 in the TME is of prognostic importance and can predict response to ICIs. Our study aimed to investigate the impact of intratumoural PD-1 and PD-L1 expression on HCC recurrence and its relation to cancer-immune phenotypes.</p><p><strong>Methods: </strong>Immunohistochemical staining was performed on archival tissue from 93 HCC, using the antibodies NAT105 (PD-1) and Ventana SP263 (PD-L1). Tumours were classified as immunologically active, excluded, or deserted. PD-1 and PD-L1 immunoreactivity was evaluated as the proportion of positive immune cells compared to the total immune cells (0%, <1%, and >1%).</p><p><strong>Results: </strong>HCC with PD-1 expression in >1% of immune cells had a significantly lower recurrence rate than tumours with <1% PD-1 expression (78%; 38/49, p = 0.027). HCC classified as immune active was also enriched for PD-1 expression >1% (77%; 48/62). Tumours with both characteristics had a significantly lower recurrence rate (p = 0.039).</p><p><strong>Conclusion: </strong>PD-1 expression on immune cells is associated with a lower recurrence rate in HCC, suggesting a role in HCC recurrence. The therapeutic use of adjuvant anti-PD-1 antibodies should thus be viewed critically and investigated further.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"157-168"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557254","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":"Deciphering WNT Signalling Vulnerabilities in Soft Tissue Sarcoma.","authors":"Marina Pérez-Capó, Esther Martinez-Font, Elena Prados, Rafael Ramos, Raúl Sánchez Morillas, Maria Rosa Martorell, Oliver Vögler, Regina Alemany, Antònia Obrador-Hevia","doi":"10.1159/000544933","DOIUrl":"10.1159/000544933","url":null,"abstract":"<p><strong>Introduction: </strong>Soft tissue sarcomas (STSs) are a group of rare malignancies with limited treatment options and a persistent lack of effective therapies. Despite the heterogeneous nature of STS, the canonical WNT/β-catenin signalling pathway has been associated with sarcomagenesis and also with the initiation and progression of other cancers.</p><p><strong>Methods: </strong>Eight patient-derived primary cultures representing different STS histological subtypes were characterized by immunohisto(cyto)chemistry, WNT/β-catenin activation and next-generation sequencing.</p><p><strong>Results: </strong>Elevated levels of active phospho-β-catenin and its nuclear localization were found in all STS primary cultures, with heterogeneous downstream WNT signalling activation. Genomic analysis of matched STS tumours identified pathogenic or likely pathogenic genetic variants in crucial signalling pathways, including WNT, DNA damage repair, and PI3K/AKT/mTOR-MAPK pathways. Interestingly, 50% of STS tumours studied carried genetic variants in PIK3CA and PTEN genes with potential clinical significance, listed as predictive biomarkers of response to specific drugs (FDA level 3).</p><p><strong>Conclusions: </strong>This study provides valuable insights into WNT signalling vulnerabilities in STS, offering a foundation for the development of targeted therapeutic strategies and the identification of potential biomarkers for personalized treatment approaches in this challenging group of malignancies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"224-238"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670636","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":"Improved Diagnosis of Glioblastoma, IDH-Wildtype, Metastasis through Molecular and DNA Methylation Profiling: Two Case Reports.","authors":"Alexandre Bertucci, Elise Kaspi, Marylin Barrie, Laurence Schenone, Amira Amri, Alexandre Astier, Isabelle Nanni, Mario Abaji, Olivier Chinot, Patrice Roll, Emeline Tabouret, Romain Appay, Diane Frankel","doi":"10.1159/000546348","DOIUrl":"10.1159/000546348","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma, the most common primary malignant brain tumor in adults, accounts for approximately 50% of primary malignant brain tumors. Extracranial metastases are extremely rare, affecting <0.5% of patients. This article describes 2 cases where next-generation sequencing and DNA methylation profiling confirmed extracranial metastases of glioblastoma, IDH-WT.</p><p><strong>Case presentation: </strong>The first case involves a 77-year-old man who developed lung and liver mass within months of diagnosis. While both biopsies revealed undifferentiated malignant tumor, identical genetic mutations on the lung biopsy and DNA methylation profiling on the liver biopsy confirmed glioblastoma metastases. The second case details a 75-year-old woman diagnosed with glioblastoma, IDH-WT who presented diffuse bone infiltration. Bone marrow aspirate and bone marrow biopsy associated with NGS and methylation profiling confirmed glioblastoma metastasis. Both patients succumbed within 8 months.</p><p><strong>Conclusion: </strong>These cases underscore the importance of molecular diagnostics in identifying glioblastoma metastases and guiding treatment, particularly in rare presentations involving extracranial spread.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"306-314"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102404","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}