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Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer. 乳腺癌增殖标记物 MCM7 的预后和临床意义。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-08-27 DOI: 10.1159/000540790
Ayat G Lashen, Michael S Toss, Catrin S Rutland, Andrew R Green, Nigel P Mongan, Emad Rakha
{"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":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-10"},"PeriodicalIF":3.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deciphering Breast Origin in Malignant Effusions: The Diagnostic Utility of an MGP, GATA-3, and TRPS-1 Immunocytochemical Panel. 解密恶性积液的乳腺起源:MGP、GATA-3 和 TRPS-1 免疫细胞化学小组的诊断效用。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-08-27 DOI: 10.1159/000540989
So Hyeon Yang, Jae Seok Lee, Ji Won Koh, Ilias P Nikas, Eun Na Kim, Hyebin Lee, Han Suk Ryu
{"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":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2024-08-27","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}
引用次数: 0
KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis. 在评估低级别乳头状尿路上皮肿瘤时,KRT18 是尿路乳头状瘤的新型生物标记物:双中心分析
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-08-27 DOI: 10.1159/000540926
Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu
{"title":"KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis.","authors":"Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu","doi":"10.1159/000540926","DOIUrl":"10.1159/000540926","url":null,"abstract":"<p><strong>Introduction: </strong>Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood.</p><p><strong>Methods: </strong>We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry.</p><p><strong>Results: </strong>In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis.</p><p><strong>Conclusion: </strong>This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-12"},"PeriodicalIF":3.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081176","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}
引用次数: 0
Prognostic Value of Cancer-Associated Fibroblast Marker Expression in the Intratumoral and Marginal Areas of Soft Tissue Sarcoma. 软组织肉瘤瘤内和边缘区域 CAF 标记表达的预后价值。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-07-22 DOI: 10.1159/000539855
Michinobu Umakoshi, Yukitsugu Kudo-Asabe, Hiroyuki Tsuchie, Zhuo Li, Kei Koyama, Ken Miyabe, Makoto Yoshida, Hiroyuki Nagasawa, Hiroshi Nanjo, Kyoji Okada, Daichi Maeda, Naohisa Miyakoshi, Masamitsu Tanaka, Akiteru Goto
{"title":"Prognostic Value of Cancer-Associated Fibroblast Marker Expression in the Intratumoral and Marginal Areas of Soft Tissue Sarcoma.","authors":"Michinobu Umakoshi, Yukitsugu Kudo-Asabe, Hiroyuki Tsuchie, Zhuo Li, Kei Koyama, Ken Miyabe, Makoto Yoshida, Hiroyuki Nagasawa, Hiroshi Nanjo, Kyoji Okada, Daichi Maeda, Naohisa Miyakoshi, Masamitsu Tanaka, Akiteru Goto","doi":"10.1159/000539855","DOIUrl":"10.1159/000539855","url":null,"abstract":"<p><strong>Introduction: </strong>The tumor microenvironment of sarcomas has not been studied in detail; in particular, little is known about cancer-associated fibroblasts (CAFs). Sarcoma cells are difficult to distinguish from CAFs, either histomorphologically or immunohistochemically.</p><p><strong>Methods: </strong>We scored the expression of individual CAF markers (fibroblast-activating protein [FAP], CD10, and podoplanin) in the intratumoral and marginal areas of 133 sarcomas. We also examined the association between these markers, as well as the number of CD163-positive macrophages (i.e., tumor-associated macrophages), and clinical outcome.</p><p><strong>Results: </strong>In all cases, the log-rank test revealed that those with high marker scores and macrophage counts (except for marginal CD10+ CAFs) showed significantly worse disease-free survival (DFS). Grade 2/3 cases with high CAF scores (excluding the marginal FAP and CD10 scores) showed significantly worse DFS, whereas those with high intratumoral FAP/CD10 and marginal podoplanin scores showed significantly worse metastasis-free survival (MFS), and those with high intratumoral CD10 score showed significantly worse local recurrence-free survival (LFS). Multivariate analysis identified intratumoral CD10/podoplanin scores and marginal FAP/podoplanin scores as independent prognostic factors for DFS, intratumoral FAP/CD10 and marginal FAP/podoplanin/CD163-positive macrophage scores as independent prognostic factors for MFS, and the intratumoral podoplanin score as an independent prognostic factor for LFS. There was a weak-to-moderate correlation between each score and CD163-positive macrophage counts.</p><p><strong>Conclusion: </strong>Patients with high CAF marker expression in the intratumoral and marginal areas have a poorer outcome.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-17"},"PeriodicalIF":3.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535056","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}
引用次数: 0
Expanding the Spectrum of Sarcoma with an Internal Tandem Duplication of BCOR: A Non-Pediatric Nasosinusal Case. 扩大 BCOR 内部串联重复肉瘤的范围:一例非儿童鼻咽癌病例。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-05-08 DOI: 10.1159/000539239
Florian Piques, Martin Penicaud, Wassim Essamet, Simon Cabello-Aguilar, Aude Trinquet, Julie A Vendrell, Valérie Costes, Jérôme Solassol
{"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":" ","pages":"370-374"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","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}
引用次数: 0
Exploration of the Tumour Biological Significance of PCLO in Gastric Cancer: Results from a Large Central European Cohort. 探讨PCLO在癌症中的肿瘤生物学意义-来自中欧大型队列的结果。
IF 5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-11-07 DOI: 10.1159/000534889
Maximilian Bernhardt, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken
{"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":" ","pages":"187-195"},"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}
引用次数: 0
ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer. ATF4 作为雌激素受体阳性乳腺癌的预后标志和谷氨酰胺代谢调节剂
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-06-11 DOI: 10.1159/000539564
Roshni Patel, Lutfi H Alfarsi, Rokaya El-Ansari, Brendah K Masisi, Busra Erkan, Ali Fakroun, Ian O Ellis, Emad A Rakha, Andrew R Green
{"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 < 0.01) and SLC7A11 (p < 0.02). High ATF4 and SLC1A5 protein expression was significantly associated with shorter breast cancer-specific survival (p < 0.01), especially in ER+ tumours (p < 0.01), while high ATF4 and SLC7A11 protein expression was associated with shorter survival (p < 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":" ","pages":"411-421"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614298/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Establishment and Characterization of Salivary Gland-Specific Injury in Transgenic Mice Model. 建立唾液腺特异性损伤转基因小鼠模型并确定其特征。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-07-24 DOI: 10.1159/000539967
Daisuke Omagari, Ryoko Ushikoshi-Nakayama, Tomoe Yamazaki, Hiroko Inoue, Kana Bando, Naoyuki Matsumoto, Ichiro Saito
{"title":"Establishment and Characterization of Salivary Gland-Specific Injury in Transgenic Mice Model.","authors":"Daisuke Omagari, Ryoko Ushikoshi-Nakayama, Tomoe Yamazaki, Hiroko Inoue, Kana Bando, Naoyuki Matsumoto, Ichiro Saito","doi":"10.1159/000539967","DOIUrl":"10.1159/000539967","url":null,"abstract":"<p><strong>Introduction: </strong>Many mouse models for autoimmune diseases also have lesions in non-target organs, which may make it difficult to determine whether the target organ lesion is primary or secondary. Hyposalivation has conventionally been studied using genetically modified mouse models for Sjogren's syndrome as well as spontaneous autoimmune mice with systemic lesions, none of which has salivary gland-specific injury.</p><p><strong>Methods: </strong>In this study, we established a salivary gland-specific injury mouse model using the toxin receptor-mediated cell knockout (TRECK) system by gene modification with the transgene composed of the 5' untranslated region of human salivary mucin gene MUC7 (highly expressed specifically in human salivary gland) inserted at the upstream of hHB-EGF (diphtheria toxin receptor) in the TRECK vector.</p><p><strong>Results: </strong>In this transgenic mouse model, we confirmed salivary gland-specific expression of hHB-EGF gene, and hyposalivation after treatment with diphtheria toxin. Histological assessment of the salivary gland from these mice showed granular convoluted tubule epithelial cells destruction at the same position as a positivity in TUNEL assay.</p><p><strong>Conclusion: </strong>This transgenic mouse model may become a useful tool for elucidating the mechanisms involved in hyposalivation and for developing pharmaceuticals and tissue regenerative medical products for this condition.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"434-441"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760281","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}
引用次数: 0
Identification of Early Events in Serrated Pathway Colorectal Tumorigenesis by Using Digital Spatial Profiling. 利用数字空间图谱鉴定锯齿状通路结直肠肿瘤发生的早期事件。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-06-05 DOI: 10.1159/000539612
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
{"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":" ","pages":"393-410"},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614314/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Low-Grade Adenosquamous Carcinoma of the Breast Masquerading as a Fibroepithelial Lesion on Core Biopsy: A Challenging Case. 在核心活检中伪装成纤维上皮病变的低级别乳腺腺鳞癌:一个棘手的病例。
IF 3.5 4区 医学
Pathobiology Pub Date : 2024-01-01 Epub Date: 2024-07-17 DOI: 10.1159/000540029
Natthawadee Laokulrath, Esther Chuwa, Mihir Gudi, Puay Hoon Tan
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