Pathobiology最新文献

{"title":"Tumor-Intrinsic Perinuclear LOXL2: Prognostic Relevance and Relationship with YAP1 Activation Status in Oral Squamous Cell Carcinoma.","authors":"Juan P Rodrigo, Gema Moreno-Bueno, Paloma Lequerica-Fernández, Tania Rodríguez-Santamarta, Eva Díaz, Llara Prieto-Fernández, Saúl Álvarez-Teijeiro, Juana M García-Pedrero, Juan Carlos de Vicente","doi":"10.1159/000539928","DOIUrl":"10.1159/000539928","url":null,"abstract":"<p><strong>Introduction: </strong>Lysyl oxidase-like 2 (LOXL2) expression and function is frequently altered in different cancers but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling.</p><p><strong>Methods: </strong>Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed.</p><p><strong>Results: </strong>Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%) and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates, and perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation. Patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS.</p><p><strong>Conclusion: </strong>Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458532","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":"Multiplex Intraoperative Rapid Immunohistochemistry with Noncontact Antibody Mixing for Distinguishing the Histologic Phenotype of Lung Cancer.","authors":"Shoji Kuriyama, Kazuhiro Imai, Hiroshi Nanjo, Yuki Wakamatsu, Shinogu Takashima, Tsubasa Matsuo, Hidenobu Iwai, Ryo Demura, Haruka Suzuki, Yuzu Harata, Sumire Shibano, Akiyuki Wakita, Yusuke Sato, Kyoko Nomura, Yoshihiro Minamiya","doi":"10.1159/000539640","DOIUrl":"10.1159/000539640","url":null,"abstract":"<p><strong>Introduction: </strong>Determining a surgical strategy for early-stage lung cancer requires an accurate histologic diagnosis. Immunohistochemistry (IHC) enables reliable diagnosis of histological types but requires more time and more tumor tissue slides than hematoxylin and eosin staining. We aimed to assess the clinical validity of a new rapid multiplex IHC technique utilizing alternating current (AC) mixing for intraoperative lung cancer diagnosis.</p><p><strong>Methods: </strong>Forty-three patients who underwent radical resection of lung cancers were enrolled in a retrospective observational study. Frozen sections were prepared from lung tumor samples, and rapid IHC employing AC mixing was implemented alongside a multiplex IHC protocol targeting thyroid transcription factor-1 + cytokeratin 5, desmoglein 3 + Napsin A, and p63 + tripartite motif containing 29. We then evaluated the concordance between intraoperative diagnoses derived from rapid multiplex IHC and final pathology.</p><p><strong>Results: </strong>The concordance rate between the pathological diagnosis made with added rapid multiplex IHC and the final pathology was 93.0% (Cohen's 𝜅 coefficient = 0.860 and 95% CI: 0.727-0.993). When considering only adenocarcinoma and squamous cell carcinoma, the diagnoses were in agreement for all cases.</p><p><strong>Conclusions: </strong>We suggest rapid multiplex IHC as a promising tool for determining surgical strategies for lung tumors.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458531","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":"ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer.","authors":"Roshni Patel, Lutfi H Alfarsi, Rokaya El-Ansari, Brendah K Masisi, Busra Erkan, Ali Fakroun, Ian O Ellis, Emad A Rakha, Andrew R Green","doi":"10.1159/000539564","DOIUrl":"10.1159/000539564","url":null,"abstract":"<p><strong>Introduction: </strong>ATF4, a stress-responsive transcription factor that upregulates adaptive genes, is a potential prognostic marker and modulator of glutamine metabolism in breast cancer. However, its exact role remains to be elucidated.</p><p><strong>Methods: </strong>ATF4 expression was evaluated at genomic and transcriptomic levels using METABRIC (n = 1,980), GeneMiner (n = 4,712), and KM-Plotter datasets. Proteomic expression was assessed via immunohistochemistry (n = 2,225) in the Nottingham Primary Breast Cancer Series. ATF4 genomic copy number (CN) variation and mRNA/protein in association with clinicopathological parameters, amino acid transporters (AATs), and patient outcome were investigated.</p><p><strong>Results: </strong>Genomic, transcriptomic, and proteomic overexpression of ATF4 was associated with more aggressive ER-negative tumours. ATF4 mRNA and protein expression were significantly associated with increased expression of glutamine related AATs including SLC1A5 (p &lt; 0.01) and SLC7A11 (p &lt; 0.02). High ATF4 and SLC1A5 protein expression was significantly associated with shorter breast cancer-specific survival (p &lt; 0.01), especially in ER+ tumours (p &lt; 0.01), while high ATF4 and SLC7A11 protein expression was associated with shorter survival (p &lt; 0.01).</p><p><strong>Conclusion: </strong>These findings suggest a complex interplay between ATF4 and AATs in breast cancer biology and underscore the potential role for ATF4 as a prognostic marker in ER+ breast cancer, offering a unique opportunity for risk stratification and personalized treatment strategies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306502","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":"Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling.","authors":"Min-Cheng Su, Ching-Hsiang Hsu, Ko-Chen Chen, Jun-Ru Lin, Huei-Ying Li, Yi-Ting Fang, Ruby Yun-Ju Huang, Yung-Ming Jeng","doi":"10.1159/000539612","DOIUrl":"10.1159/000539612","url":null,"abstract":"<p><strong>Introduction: </strong>The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma.</p><p><strong>Methods: </strong>We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal cancer (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC.</p><p><strong>Results: </strong>Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities.</p><p><strong>Conclusion: </strong>These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237299","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":"Comparison of Breast Fine-Needle Aspiration Cytology and Tissue Sampling for High-Throughput Proteomic Analysis and Cancer Biomarker Detection.","authors":"Hye Eun Park, Dohyun Han, Jae Seok Lee, Ilias P Nikas, Hyeyoon Kim, Sohyeon Yang, Hyebin Lee, Han Suk Ryu","doi":"10.1159/000539478","DOIUrl":"10.1159/000539478","url":null,"abstract":"<p><strong>Introduction: </strong>Fine-needle aspiration cytology (FNAC) specimens are widely utilized for the diagnosis and molecular testing of various cancers. We performed a comparative proteomic analysis of three different sample types, including breast FNAC, core needle biopsy (CNB), and surgical resection tissues. Our goal was to evaluate the suitability of FNAC for in-depth proteomic analysis and for identifying potential therapeutic biomarkers in breast cancer.</p><p><strong>Methods: </strong>High-throughput proteomic analysis was conducted on matched FNAC, CNB, and surgical resection tissue samples obtained from breast cancer patients. The protein identification, including currently established or promising therapeutic targets, was compared among the three different sample types. Gene Ontology (GO) enrichment analysis was also performed on all matched samples.</p><p><strong>Results: </strong>Compared to tissue samples, FNAC testing revealed a comparable number of proteins (7,179 in FNAC; 7,196 in CNB; and 7,190 in resection samples). Around 85% of proteins were mutually identified in all sample types. FNAC, along with CNB, showed a positive correlation between the number of enrolled tumor cells and identified proteins. In the GO analysis, the FNAC samples demonstrated a higher number of genes for each pathway and GO terms than tissue samples. CCND1, CDK6, HER2, and IGF1R were found in higher quantities in the FNAC compared to tissue samples, while TUBB2A was only detected in the former.</p><p><strong>Conclusion: </strong>FNAC is suitable for high-throughput proteomic analysis, in addition to an emerging source that could be used to identify and quantify novel cancer biomarkers.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180365","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":"Decreasing Albumin mRNA Expression in Cholangiocarcinomas along the Bile Duct Tree.","authors":"Elisa Albertini, Stefano Chillotti, Giada Monti, Deborah Malvi, Marzia Deserti, Alessio Degiovanni, Andrea Palloni, Simona Tavolari, Giovanni Brandi, Antonia D'Errico, Francesco Vasuri","doi":"10.1159/000538706","DOIUrl":"10.1159/000538706","url":null,"abstract":"<p><strong>Introduction: </strong>The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree.</p><p><strong>Methods: </strong>Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic. Histology was revised in all cases, and albumin ISH was automatically performed by the RNAscope®.</p><p><strong>Results: </strong>ISH was always negative in extrahepatic CCAs, only 1 perihilar case was positive, and any positivity was observed in 25/29 (86.2%) intrahepatic CCAs (p &lt; 0.001). Concerning CCA subtypes, mean cell positivity was 38.8 ± 29.8% in small-duct CCAs and 11.4 ± 21.9 in large-duct CCAs, respectively (p = 0.003); 12/15 (80.0%) small-duct and 3/14 (21.4%) large-duct CCAs showed &gt;5% positive cells (p = 0.002; odds ratio 14.7).</p><p><strong>Conclusions: </strong>The introduction of more sensitive techniques changed the indications for ISH since most small-duct intrahepatic CCAs show diffuse positivity. Albumin positivity decreases from liver periphery to the large ducts, suggesting that ISH can be helpful in the differential diagnosis between small-duct and large-duct CCAs, as well as between intrahepatic large-duct CCAs and metastases.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065620","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":"Expanding the Spectrum of Sarcoma with an Internal Tandem Duplication of BCOR: A Non-Pediatric Nasosinusal Case.","authors":"Florian Piques, Martin Penicaud, Wassim Essamet, Simon Cabello-Aguilar, Aude Trinquet, Julie A Vendrell, Valérie Costes, Jérôme Solassol","doi":"10.1159/000539239","DOIUrl":"10.1159/000539239","url":null,"abstract":"<p><strong>Introduction: </strong>Undifferentiated small round-cell sarcomas with BCL6 corepressor (BCOR) alterations, such as an internal tandem duplication (ITD) within exon 15, are typically described as a pediatric group of Ewing-like small round-cell sarcomas.</p><p><strong>Case presentation: </strong>In contrast to this notion, we report the case of a 71-year-old woman with a nasosinusal sarcoma featuring a BCOR ITD. To the best of our knowledge, this presence had not been previously documented in a sarcoma of the nasal and sinus cavities in an elderly patient. The identified duplication shares a similar minimal critical region as described in clear-cell sarcomas of the kidney in children. This alteration, located within the PCGF1 binding domain, is believed to disrupt the activity of PRC1.1.</p><p><strong>Conclusion: </strong>This case underscores the need for in-depth research into the molecular biology of these rare tumors and explores potential alternative treatment options. The patient achieved remission after two cycles of doxorubicin and cyclophosphamide chemotherapy, highlighting the promise of potential therapeutic options for BCOR ITD sarcomas.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892194","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":"Clinically Applicable Pan-Origin Cancer Detection for Lymph Nodes via Artificial Intelligence-Based Pathology.","authors":"Yi Pan, Hongtian Dai, Shuhao Wang, Lang Wang, Qiting Li, Wenmiao Wang, Jiangtao Li, Dan Qi, Zhaoyang Yang, Jia Jia, Yaxi Wang, Qing Fang, Lin Li, Weixun Zhou, Zhigang Song, Shuangmei Zou","doi":"10.1159/000539010","DOIUrl":"10.1159/000539010","url":null,"abstract":"<p><strong>Introduction: </strong>Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent.</p><p><strong>Methods: </strong>Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole-slide images (WSIs) and is composed of two deep learning models to locate the lymph nodes and detect cancers.</p><p><strong>Results: </strong>It achieved an area under the receiver operating characteristic curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 WSIs from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical centre, with an AUC of 0.925.</p><p><strong>Conclusion: </strong>Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892189","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":"Characterization of Pleural Mesothelioma by Hierarchical Clustering Analyses Using Immune Cells within Tumor Microenvironment.","authors":"Shingo Inaguma, Chengbo Wang, Sunao Ito, Akane Ueki, Jerzy Lasota, Piotr Czapiewski, Renata Langfort, Janusz Rys, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, Shuji Takiguchi, David S Schrump, Markku Miettinen, Satoru Takahashi","doi":"10.1159/000538520","DOIUrl":"10.1159/000538520","url":null,"abstract":"<p><strong>Introduction: </strong>Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated.</p><p><strong>Methods: </strong>In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers: CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1, and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed.</p><p><strong>Results: </strong>Among the immune cell markers, CD3 (p &lt; 0.0001), CD4 (p = 0.0016), CD8 (p = 0.00094), CD163+ (p = 0.042), and FOXP3+ (p = 0.025) were significantly associated with an unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (p = 0.050), CD27 (p = 0.014), and TIM-3 (p = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (p = 0.016): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (p = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04), and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients.</p><p><strong>Conclusion: </strong>Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288718","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":"Exploration of the Tumour Biological Significance of PCLO in Gastric Cancer: Results from a Large Central European Cohort.","authors":"Maximilian Bernhardt, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken","doi":"10.1159/000534889","DOIUrl":"10.1159/000534889","url":null,"abstract":"<p><strong>Introduction: </strong>A recent multiregional whole-exome sequencing of 48 tumour samples from 9 gastric adenocarcinomas discovered PCLO mutations in 23 (47.9%) tumour samples. Based on that unexpected high prevalence of PCLO mutations, we hypothesized a tumour biological significance of PCLO in gastric cancer (GC).</p><p><strong>Methods: </strong>Tumour samples (whole tissue sections) obtained from 466 patients resected for therapy-naive GC were stained with an anti-PCLO antibody. The histoscore for tumour cells and the presence of immunostaining of stromal cells and tumour vessels was documented for each case. An algorithm for PCLO immunopositivity was formed and correlated with clinicopathological patient characteristics.</p><p><strong>Results: </strong>175 GCs were classified as PCLO positive within tumour cells, and 291 as negative. Stromal cells were positive for PCLO in 106 cases and tumour vessels in 84. PCLO-positive GCs more often showed an intestinal phenotype, a lower T category and were more commonly associated with Helicobacter pylori infection. A separate analysis of PCLO expression in intestinal and diffuse type GCs, respectively, showed no significant correlations. Patients with PCLO negative/low tumour cells showed a shortened overall (14.0 ± 1.4 vs. 16.0 ± 1.8 months) and tumour-specific survival (15.0 ± 1.6 months vs. 17.9 ± 3.6). Comparison of PCLOs genotype with its phenotype in 48 tumour samples obtained from nine cases showed no direct correlations with missense mutations.</p><p><strong>Conclusion: </strong>Our data provide evidence that PCLO is differentially expressed in GC and might delay tumour progression.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11126201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484696","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}