Pathobiology最新文献

{"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":"https://doi.org/10.1159/000544933","url":null,"abstract":"<p><strong>Introduction: </strong>Soft tissue sarcomas (STS) 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 (NGS).</p><p><strong>Results: </strong>Elevated levels of active phospho-β-catenin and its nuclear localization was found in all STS primary cultures, with heterogeneous downstream WNT signaling activation. Genomic analysis of matched STS tumors identified pathogenic or likely pathogenic genetic variants in crucial signaling pathways, including WNT, DNA damage repair and PI3K/AKT/mTOR-MAPK pathways. Interestingly, 50% of STS tumors 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 signaling 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":"1-20"},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","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":"The Role of CK7 and CK19 immunohistochemistry in the Evaluation of HPV-induced Cervical Squamous Precursor Epithelial Lesions.","authors":"Fatma Al Hinai, Ruqaiya Al Shamsi, Samya Al Husaini, Afrah Al Rashdi, Mohammad Arafa","doi":"10.1159/000545229","DOIUrl":"https://doi.org/10.1159/000545229","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is the fourth common cancer in women worldwide. In most cases, the disease is induced by persistent high risk Human Papilloma Virus (HPV) infection. This study aimed to assess the role of CK7 and CK19 in human papillomavirus (HPV) induced cervical epithelial lesions using tissue microarray (TMA).</p><p><strong>Methods: </strong>A retrospective cohort study included females with cervical low-grade and high-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC). TMA was constructed using specimens of 270 cases and 233 control tissues. CK7 and CK19 immunohistochemistry was scored as negative or positive. Follow-up information was gathered.</p><p><strong>Results: </strong>CK7 was negative in about 85% of LSILs and positive in 55% of HSILs (p<0.001). CK19 showed positivity in about 50% of LSILs and 77% of the HSILs (p<0.001). For cases with available follow-up data, about 69% of CK7 positive LSILs progressed to higher grade lesions and 64% of CK7 positive HSILs showed progression to higher grades (CIN2 to CIN3) or to SCC. Regarding CK19, nearly 66% positive LSILs progressed to HSIL whereas, 62% of positive HSILs showed progression. LSILs with positivity for both markers progressed to HSIL in 70% of cases.</p><p><strong>Conclusions: </strong>CK7 and Ck19 positivity is significantly associated with higher-grade HPV-induced cervical lesions. Lesions with combined CK7 and CK19 positivity have a higher risk of progression to higher grade lesions.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-16"},"PeriodicalIF":3.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625205","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":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Significance of Programmed Cell Death-1, Programmed Cell Death-Ligand 1, Programmed Cell Death-Ligand 2, and Fibroblast Growth Factor Receptor 3 mRNA Expression in Bladder Cancer.","authors":"Ana Blanca, Antonio Lopez-Beltran, Enrique Gomez-Gomez, Pablo Campos-Hernández, Alessia Cimadamore, Rodolfo Montironi, Liang Cheng","doi":"10.1159/000544733","DOIUrl":"10.1159/000544733","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the prognostic significance of programmed cell death (PD)-1/PD-ligand 1 (PD-L1), PD-ligand 2 (PD-L2), and fibroblast growth factor receptor 3 (FGFR3) expression in bladder cancer (BC).</p><p><strong>Methods: </strong>A retrospective study was conducted on BC patients who underwent transurethral resection between 2005 and 2014. Of the initial 136 patients, 31 were excluded for not meeting the inclusion criteria, leaving 105 cases for the final analysis. The mRNA levels of PD-1/PD-L1/PD-L2 and FGFR3 were assessed using quantitative reverse transcription PCR and NanoString technology.</p><p><strong>Results: </strong>High expression of PD-1 and its ligands (PD-L1/PD-L2) showed a strong correlation with each other and was associated with poor clinical outcomes, including higher tumor stage, grade, and cancer-specific mortality (p < 0.001). Conversely, high FGFR3 expression was associated with improved survival and more favorable clinicopathological features. Interestingly, an inverse relationship was observed between FGFR3 and PD-1 (p = 0.032) and PD-L1 (p = 0.016) expression. High mRNA expression profiles of PD-1, PD-L1, PD-L2, and low FGFR3 expression were associated with worse cancer-specific survival (p < 0.001). Multivariate analysis revealed that advanced stage, low FGFR3 expression, and high PD-L2 expression are independent predictors of poor prognosis in BC patients.</p><p><strong>Conclusion: </strong>Our findings suggest that elevated levels of PD-1, PD-L1, and PD-L2, combined with reduced FGFR3 expression, may assist in identifying patients with poor outcomes and highlight their potential as prognostic biomarkers in BC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-14"},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516278","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":"Novel Role of Microtubule-Associated Serine/Threonine Kinase Like as a Good Prognostic Factor in Oral Squamous Cell Carcinoma and Evidences for a Link with Smad7.","authors":"Esperanza Pozo-Agundo, Miguel Álvarez-González, Paloma Lequerica-Fernández, Sergi Herrera I Nogués, Juan Pablo Rodrigo, Tania Rodríguez-Santamarta, Héctor E Torres-Rivas, Saúl Álvarez-Teijeiro, Juana María García-Pedrero, Mónica Álvarez-Fernández, Juan Carlos de Vicente","doi":"10.1159/000544183","DOIUrl":"10.1159/000544183","url":null,"abstract":"<p><strong>Introduction: </strong>Upregulated microtubule-associated serine/threonine kinase like (MASTL), a cell cycle kinase required for a progression through mitosis, expression has been associated to poor prognosis. This study aimed to investigate the clinical relevance of MASTL expression in oral squamous cell carcinoma (OSCC) and a possible mechanistic link with epithelial-mesenchymal transition (EMT).</p><p><strong>Methods: </strong>Immunohistochemical analysis of MASTL, E-cadherin, vimentin, and Smad7 was performed in paraffin-embedded tissue specimens from 148 OSCC patients.</p><p><strong>Results: </strong>Nuclear MASTL expression was detected in 115 (77.7%) OSCC specimens. High MASTL expression was significantly associated with the male gender, smoking habit, T stage, early clinical stage, and absence of vascular invasion. MASTL expression was inversely correlated with Smad7, whereas no association was observed with E-cadherin and vimentin. Patients harboring tumors with low MASTL expression exhibited a poorer overall survival. Smad7 expression was significantly related to reduced disease-specific and overall survival. High levels of MASTL expression were associated with better prognosis in T3 patients, N0 cases, and patients treated by surgery combined with radiotherapy and chemotherapy.</p><p><strong>Conclusion: </strong>The present study uncovers MASTL as a good prognostic factor in OSCC and a potential link with EMT via Smad7.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-13"},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516235","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":"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":"1-7"},"PeriodicalIF":3.5,"publicationDate":"2025-02-09","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":"Trop2 Expression in Correlation to the Molecular Subtype in Vulvar Squamous Cell Carcinomas.","authors":"Anne Kathrin Höhn, Benjamin Wolf, Mirjam Forberger, Christine E Brambs, Blake Gilks, Lien Hoang, Grit Gesine Ruth Hiller, Jessica N McAlpine, Amy Jamieson, Yvette Drew, Lars-Christian Horn","doi":"10.1159/000543554","DOIUrl":"10.1159/000543554","url":null,"abstract":"<p><strong>Introduction: </strong>Targeted therapy with antibody-drug conjugates (ADCs) has achieved promising results in the treatment of different solid tumors. Sacituzumab-Govitecan (SG), a humanized anti-Trop2 monoclonal antibody linked with the cytotoxic topoisomerase I inhibitor SN-38, has been approved for the treatment of metastatic triple-negative breast cancer. The treatment approach with SG requires the expression of Trop2 within the tumor cells. Trop2 is overexpressed in many other cancer types, suggesting a broader therapeutic application beyond breast cancer to these ADCs. We explore expression of Trop2 vulvar squamous cell carcinomas (VSCCs) and how this relates to molecular classification.</p><p><strong>Methods: </strong>Immunohistochemical Trop2 expression was evaluated on diagnostic biopsies of VSCC using an immunoreactive score. Staining results were compared to the molecular subtype of VSCC.</p><p><strong>Results: </strong>Fifty-seven cases were included in the study. 63.2% of VSCC were p16-ve/p53abn (HPV-independent (p53abn)) molecular subtype, 29.8% p16+ve/p53wt (HPV-associated) and 1.4% p16-ve/p53wt (HPV-independent (p53wt)) tumors. All diagnostic biopsies (N = 57) showed at least a weak Trop2 expression. Moderate and strong expression was seen in 15/17 (88.2%) of the p16-ve/p53abn, 32/36 (88.8%) of the p16+ve/p53wt and 3/4 (75%) of the p16-ve/p53wt molecular subtype. Expression was significantly higher, as assessed by H score, in the HPV-associated VSCC, compared to HPV-independent.</p><p><strong>Conclusion: </strong>VSCCs have high expression of Trop2 and represents a promising therapeutic target. Clinical trials exploring Trop2-directed ADCs such as SG are warranted in this rare cancer type, including in the prognostically poor HPV-independent VSCC with a TP53-mutation (p16-ve/p53abn molecular subtype). The targetable molecule, Trop2, can be easily assessed by immunohistochemistry on diagnostic biopsies from VSCC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-7"},"PeriodicalIF":3.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009448","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":"Gastric Adenocarcinoma with Enteroblastic Differentiation.","authors":"Ádám Ferenczi, Levente Kuthi, Anita Sejben","doi":"10.1159/000543330","DOIUrl":"10.1159/000543330","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare entity with worse prognosis compared to conventional gastric adenocarcinomas. Its histological characteristics are fetal gut-like architecture and tumor cells with cytoplasmic clearing, as well as positive immunohistochemical reaction to at least one of the enteroblastic markers. Hereby, we present a case of GAED with neuroendocrine marker positivity, with whole-exome sequencing (WES), and an updated literature review.</p><p><strong>Case presentation: </strong>A 68-year-old woman presented at the general practitioner with abdominal pain. Abdominal ultrasound described gastric wall thickening raising suspicion of gastric cancer; thus, gastroscopy was performed, and biopsy samples were taken, which confirmed malignancy. Neoadjuvant systemic chemotherapy was initiated, and total gastrectomy was performed. Microscopically, pleomorphic polygonal cells were visible with clear cytoplasm and high-grade cellular atypia. Alcian blue and PAS stains demonstrated positivity for acidic and neutral mucins. P53 IHC was negative, indicative of null-phenotype, while Syntaxin-1 and Chromogranin showed focal positivity. SALL4 and Glypican 3 were positive; however, AFP displayed only minimal, uncertain positivity. The Ki67 labeling index was 70%. Due to the morphological and immunohistochemical characteristics, the tumor was concluded as GAED with neuroendocrine marker positivity. WES was carried out revealing 4 pathogenic, including TP53, KLHL7, RAPSN, and ACTA1, and 3 likely pathogenic mutations, encompassing PNKP, HNF1A, and ADNP.</p><p><strong>Discussion: </strong>GAED is a rare subtype of gastric adenocarcinomas, representing 0.3-5.4% of all cases, and has an unclarified etiology. Our WES results identified new pathogenic and likely pathogenic mutations. From a differential diagnostic point of view, hepatoid adenocarcinoma and the possibility of metastatic origin have to be excluded.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-11"},"PeriodicalIF":3.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952803","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":"Validation of a Urine-Based Proteomics Test to Predict Clinically Significant Prostate Cancer: Complementing mpMRI Pathway.","authors":"Maria Frantzi, Ana C Morillo, Guillermo Lendinez, Ana Blanca, Daniel Lopez Ruiz, Jose Parada, Isabel Heidegger, Zoran Culig, Emmanouil Mavrogeorgis, Antonio Lopez Beltran, Marina Mora-Ortiz, Julia Carrasco-Valiente, Harald Mischak, Rafael A Medina, Pablo Campos Hernandez, Enrique Gómez Gómez","doi":"10.1159/000542465","DOIUrl":"10.1159/000542465","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PCa) is the most frequently diagnosed cancer among men. A major clinical need is to accurately predict clinically significant PCa (csPCa). A proteomics-based 19-biomarker model (19-BM) was previously developed using capillary electrophoresis-mass spectrometry (CE-MS) and validated in close to 1,000 patients at risk for PCa. This study aimed to validate 19-BM in a multicenter prospective cohort of 101 biopsy-naive patients using current diagnostic pathways.</p><p><strong>Methods: </strong>Urine samples from 101 patients with suspicious of PCa were analyzed using CE-MS. All patients underwent multiparametric or magnetic resonance imaging (mpMRI) using a 3-T system. The 19-BM score was estimated using support vector machine-based software (MosaCluster v1.7.0), employing the previously published cut-off criterion of -0.07. Diagnostic nomograms were investigated along with mpMRI.</p><p><strong>Results: </strong>Independent validation of 19-BM yielded a sensitivity of 77% and a specificity of 85% (AUC:0.81). This performance surpassed those of prostate-specific antigen (PSA; AUC:0.56) and PSA density (AUC:0.69). For PI-RADS≤ 3 patients, 19-BM showed a sensitivity of 86% and a specificity of 88%. Integrating 19-BM with mpMRI resulted in significantly better accuracy (AUC:0.90) compared to individual investigations alone (AUC19BM = 0.81; p = 0.004 and AUCmpMRI: 0.79; p = 0.001). Examining the decision curve analysis, 19-BM with mpMRI surpassed other approaches for the prevailing risk interval from a 30% cut-off.</p><p><strong>Conclusions: </strong>19-BM exhibited favorable reproducibility for the prediction of csPCa. In patients with PI-RADS ≤3, 19-BM correctly classified 88% of the patients with insignificant PCa at the cost of 1 missed csPCa patient. Utilizing the 19-BM test could prove valuable in complementing mpMRI and reducing the need for unnecessary biopsies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"99-108"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625468","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":"Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer.","authors":"Ayat G Lashen, Michael S Toss, Catrin S Rutland, Andrew R Green, Nigel P Mongan, Emad Rakha","doi":"10.1159/000540790","DOIUrl":"10.1159/000540790","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in oestrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy-treated BC patients, high MCM7 was associated with poor outcome, but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival, while patients with double low expression BC showed the best outcome compared with single expression groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"18-27"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081177","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}