Cancers最新文献

{"title":"Interfering Nuclear Protein Laminb1 Induces DNA Damage and Reduces Vemurafenib Resistance in Melanoma Cells In Vitro.","authors":"Yuan Li, Yuqing Feng, Dan Chen","doi":"10.3390/cancers16234060","DOIUrl":"https://doi.org/10.3390/cancers16234060","url":null,"abstract":"<p><strong>Background/objectives: </strong>Drug resistance poses a substantial clinical challenge in melanoma treatment, yet the underlying mechanism remains elusive. Here, we report the novel role of laminB1, a nuclear structure protein, in regulating the response of BRAF-mutated melanoma cells to vemurafenib.</p><p><strong>Results: </strong>Our analysis of clinical samples and existing databases highlights the tight correlation between the laminB1 expression level and melanoma progression and prognosis. Notably, we observe that laminB1 expression is upregulated when BRAF-mutated melanoma cells develop resistance to vemurafenib. The knockdown of laminB1 substantially increases the sensitivity of melanoma cells to vemurafenib. Furthermore, we found laminB1 suppression increases cell apoptosis via the escalation of DNA damage in a vemurafenib-dose-dependent manner. Conversely, protective cell autophagy is negatively regulated by laminB1 suppression. Interestingly, this distinct regulation pattern of apoptosis and autophagy by laminB1 cooperatively promotes the response of BRAF-mutated melanoma cells to vemurafenib.</p><p><strong>Conclusions: </strong>Our findings unveil the potential of laminB1 as both a diagnosis marker and a therapeutic target of melanoma.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TPC2: From Blond Hair to Melanoma?","authors":"Carla Abrahamian, Lina Ouologuem, Rachel Tang, Thomas Fröhlich, Karin Bartel, Christian Grimm","doi":"10.3390/cancers16234065","DOIUrl":"https://doi.org/10.3390/cancers16234065","url":null,"abstract":"<p><p>Two-pore channel 2 (TPC2) is expressed in endolysosomes throughout the human body, as well as in melanosomes of melanocytes. Melanocytes produce pigment, i.e., melanin, which determines hair and skin color but also protects from UV light. Extensive exposure to UV light is one of the major risk factors for the development of melanoma, which develops from pigment-producing cells, i.e., melanocytes. In recent years, several human TPC2 single nucleotide polymorphisms have been identified to increase the likelihood of carriers presenting with blond hair and hypopigmentation. These variants were all characterized as gain-of-function versions of TPC2. Vice versa, the loss of function of TPC2 increases melanin production and reduces cancer hallmarks such as proliferation, migration, invasion, tumor growth, and metastasis formation. The activity of TPC2 is controlled in a complex manner, with several endogenous ligands as well as a number of interacting proteins being involved. We will discuss here the role of TPC2 in pigmentation and its potential to impact melanoma development and progression and highlight recent findings on Rab7a as an enhancer of TPC2 activity.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited Thyroidectomy Achieves Equivalent Survival to Total Thyroidectomy for Early Localized Medullary Thyroid Cancer.","authors":"Jessan A Jishu, Mohammad H Hussein, Salman Sadakkadulla, Solomon Baah, Yaser Y Bashumeel, Eman Toraih, Emad Kandil","doi":"10.3390/cancers16234062","DOIUrl":"https://doi.org/10.3390/cancers16234062","url":null,"abstract":"<p><strong>Background: </strong>The optimal surgical approach for localized T1 medullary thyroid cancer remains unclear. Total thyroidectomy is standard, but lobectomy and subtotal thyroidectomy may minimize mortality while maintaining oncologic control.</p><p><strong>Methods: </strong>This retrospective analysis utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results registry to identify 2702 MTC patients including 398 patients with T1N0/1M0 MTC treated with total thyroidectomy or lobectomy/subtotal thyroidectomy from 2000 to 2019. Cox regression analyses assessed thyroid cancer-specific and overall mortality.</p><p><strong>Results: </strong>The majority (89.7%) underwent total thyroidectomy, while 10.3% had lobectomy/subtotal thyroidectomy. Nodal metastases were present in 29.6%. Over a median follow-up of 8.75 years, no significant difference was observed in cancer-specific mortality (5.7% vs. 8.1%, <i>p</i> = 0.47) or overall mortality (13.2% vs. 12.8%, <i>p</i> = 0.95). On multivariate analysis, undergoing cancer-directed surgery was associated with significantly improved overall survival (HR 0.18, <i>p</i> < 0.001) and cancer-specific survival (HR 0.17, <i>p</i> < 0.001) compared to no surgery. However, no significant survival difference was seen between total thyroidectomy and lobectomy/subtotal thyroidectomy for overall mortality (HR 0.77, <i>p</i> = 0.60) or cancer-specific mortality (HR 0.44, <i>p</i> = 0.23). The extent of surgery also did not impact outcomes within subgroups stratified by age, gender, T stage, or nodal status. Delayed surgery >1 month after diagnosis was associated with worse overall survival (<i>p</i> = 0.012).</p><p><strong>Conclusions: </strong>For localized T1 MTC, lobectomy/subtotal thyroidectomy appears to achieve comparable long-term survival to total thyroidectomy in this population-based analysis. The selective use of limited thyroidectomy may be reasonable for low-risk T1N0/1M0 MTC patients. Delayed surgery is associated with worse survival and additional neck dissection showed no benefit for this select group of patients.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synchronized Contrast-Enhanced 4DCT Simulation for Target Volume Delineation in Abdominal SBRT.","authors":"Valeria Faccenda, Denis Panizza, Rita Marina Niespolo, Riccardo Ray Colciago, Giulia Rossano, Lorenzo De Sanctis, Davide Gandola, Davide Ippolito, Stefano Arcangeli, Elena De Ponti","doi":"10.3390/cancers16234066","DOIUrl":"https://doi.org/10.3390/cancers16234066","url":null,"abstract":"<p><p><b>Background/Objectives:</b> To present the technical aspects of contrast-enhanced 4DCT (ce4DCT) simulation for abdominal SBRT. <b>Methods:</b> Twenty-two patients underwent two sequential 4DCT scans: one baseline and one contrast-enhanced with personalized delay time (<i>t_delay</i>) calculated to capture the tumor in the desired contrast phase, based on diagnostic triple-phase CT. The internal target volume (ITV) was delineated on ten contrast phases, and a panel of three experts qualitatively evaluated tumor visibility. Aortic HU values were measured to refine the <i>t_delay</i> for subsequent patients. The commonly used approach of combining triple-phase CT with unenhanced 4DCT was simulated, and differences in target delineation were evaluated by volume, centroid shift, Dice and Jaccard indices, and mean distance agreement (MDA). The margins required to account for motion were calculated. <b>Results:</b> The ce4DCT acquisitions substantially improved tumor visibility over the entire breathing cycle in 20 patients, according to the experts' unanimous evaluation. The median contrast peak time was 54.5 s, and the washout plateau was observed at 70.3 s, with mean peak and plateau HU values of 292 ± 59 and 169 ± 25. The volumes from the commonly used procedure (ITV2) were significantly smaller than the ce4DCT volumes (ITV1) (<i>p</i> = 0.045). The median centroid shift was 4.7 mm. The ITV1-ITV2 overlap was 69% (Dice index), 53% (Jaccard index), and 2.89 mm (MDA), with the liver volumes showing significantly lower indices compared to the pancreatic volumes (<i>p</i> ≤ 0.011). The margins required to better encompass ITV1 were highly variable, with mean values ≥ 4 mm in all directions except for the left-right axis. <b>Conclusions:</b> The ce4DCT simulation was feasible, resulting in optimal tumor enhancement with minimal resource investment, while significantly mitigating uncertainties in SBRT planning by addressing poor visibility and respiratory motion. Triple-phase 3DCT with unenhanced 4DCT led to high variability in target delineation, making the isotropic margins ineffective.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Versican Proteolysis by ADAMTS: Understanding Versikine Expression in Canine Spontaneous Mammary Carcinomas.","authors":"Maria Carolina Souza, Simone Nunes, Samantha Hellen Santos Figuerêdo, Bruno Sousa de Almeida, Isac Patrick Conceição Santos, Geovanni Dantas Cassali, Sérgio Marcos Arruda, Thiago Marconi de Souza Cardoso, Alessandra Estrela-Lima, Karine Araújo Damasceno","doi":"10.3390/cancers16234057","DOIUrl":"https://doi.org/10.3390/cancers16234057","url":null,"abstract":"<p><p><b>Background:</b> The present study investigates VKINE, a bioactive proteolytic fragment of the proteoglycan VCAN, as a novel and significant element in the tumor extracellular matrix (ECM). Although VKINE has been recognized for its immunomodulatory potential in certain tumor types, its impact on ECM degradation and prognostic implications remains poorly understood. <b>Objectives</b>: This study aimed to evaluate VCAN proteolysis and its association with ADAMTS enzymes involved in extracellular matrix remodeling in spontaneous canine mammary gland cancer. <b>Methods</b>: The expression levels of VKINE, ADAMTS enzymes, and collagen fibers were comparatively analyzed in situ and in invasive areas of carcinoma in mixed tumor (CMT) and carcinosarcoma (CSS) with different prognoses. <b>Results</b>: VKINE was notably expressed in the stroma adjacent to the invasion areas in CMT, whereas ADAMTS-15 was identified as the enzyme associated with VCAN proteolysis. Inverse correlations were observed between type III collagen and VCAN expression in in situ areas. <b>Conclusions</b>: Our findings suggest that VKINE and ADAMTS-15 play crucial roles in the tumor microenvironment, influencing invasiveness and type III collagen deposition. This study contributes to a better understanding of the dynamics within the ECM, paving the way for potential new tools in diagnosing and treating human and canine mammary tumors.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Novel HDAC Inhibitor OBP-801 Promotes MHC Class I Presentation Through LMP2 Upregulation, Enhancing the PD-1-Targeting Therapy in Clear Cell Renal Cell Carcinoma.","authors":"Tsukasa Narukawa, Shusuke Yasuda, Mano Horinaka, Keiko Taniguchi, Takahiro Tsujikawa, Mie Morita, Osamu Ukimura, Toshiyuki Sakai","doi":"10.3390/cancers16234058","DOIUrl":"https://doi.org/10.3390/cancers16234058","url":null,"abstract":"<p><strong>Background: </strong>Histone deacetylase (HDAC) inhibitors have been reported to exhibit immunomodulatory activities, including the upregulation of major histocompatibility complex class I (MHC class I). Although the immunoproteasome plays a pivotal role in MHC class I antigen presentation, its effect on immunotherapy for clear cell renal cell carcinoma (ccRCC) remains unclear.</p><p><strong>Methods: </strong>This study assessed whether OBP-801, a novel HDAC inhibitor, affects the expression of immunoproteasome subunits and subsequently the MHC class-I-mediated anti-cancer immunity in ccRCC. We analyzed the data of 531 patients with ccRCC from the Cancer Genome Atlas Kidney Clear Cell Carcinoma database. We further evaluated the treatment efficacy of the combination of OBP-801 and anti-PD-1 in a ccRCC mouse model.</p><p><strong>Results: </strong>Low molecular mass polypeptide (LMP) 2 was correlated most positively with CD3E, CD8A, and CD8B expression and estimated CD8⁺ T cell number. In vitro studies showed that OBP-801 upregulated MHC class I presentation by inducing LMP2 expression in the ccRCC cell lines RENCA, 786-O, and Caki-1. In vivo studies in a syngeneic mouse model with subcutaneous implantation of RENCA cells showed that OBP-801 treatment increased the percentage of CD45⁺CD3e⁺ T cells in tumor-infiltrating lymphocytes. The combination of anti-PD-1 antibody and OBP-801 enhanced the anti-tumor effect, LMP2 protein expression, and MHC class I presentation in tumor cells. MHC class I presentation in the tumors of each mouse was positively correlated with the percentage of CD45⁺CD3e⁺ T cells.</p><p><strong>Conclusions: </strong>Our results demonstrate that OBP-801 promotes MHC class I presentation through LMP2 upregulation in tumor cells and thereby potentiates PD-1-targeting therapy. These data suggest that the combination of OBP-801 and anti-PD-1 treatment is a promising therapeutic strategy for ccRCC.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-Modified Glasgow Prognostic Score Predicts Therapeutic Effect of Pembrolizumab in Recurrent and Metastatic Head and Neck Cancer.","authors":"Natsuko Ueda, Masashi Kuroki, Hirofumi Shibata, Manato Matsubara, Saki Akita, Tatsuhiko Yamada, Rina Kato, Ryota Iinuma, Ryo Kawaura, Hiroshi Okuda, Kosuke Terazawa, Kenichi Mori, Ken Saijo, Toshimitsu Ohashi, Takenori Ogawa","doi":"10.3390/cancers16234056","DOIUrl":"https://doi.org/10.3390/cancers16234056","url":null,"abstract":"<p><strong>Background: </strong>Previously, we proposed that the immune-modified Glasgow Prognostic Score (imGPS), which adds the lymphocyte count to the mGPS, is helpful as a prognostic marker for patients with head and neck squamous cell carcinoma. In this study, we investigated the imGPS as a marker for the therapeutic effect of pembrolizumab in treating recurrent and metastatic head and neck cancer (RMHNC).</p><p><strong>Methods: </strong>This study included RMHNC patients who were treated with pembrolizumab from December 2019 to April 2024. ALB, CRP, lymphocyte counts, neutrophil-to-lymphocyte ratios (NLRs), mGPSs, and imGPSs were extracted as biomarkers, and the response rate and prognosis were analyzed for each.</p><p><strong>Results: </strong>A total of 54 patients were enrolled. Lymphocyte counts were correlated with the overall response rates (ORRs) (<i>p</i> = 0.0082). Although the mGPS did not show significant differences in ORRs, imGPSs revealed a significant difference (<i>p</i> = 0.013). CRP, ALB, and lymphocyte counts were correlated with overall survival (OS) and/or progression-free survival (PFS). NLRs, mGPSs, and imGPSs were also correlated with OS and/or PFS, with imGPSs showing the greatest area under the curve (OS; AUC = 0.795, PFS; AUC = 0.754).</p><p><strong>Conclusions: </strong>This study demonstrates that the imGPS is an excellent predictive marker for the therapeutic effect and prognosis of pembrolizumab for RMHNC. The imGPS can be employed with daily blood tests, highlighting the potential to forecast the impact of the ICI with high reliability.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Outcomes of 5-Fluorouracil-Related Early-Onset Toxicities: A Retrospective Cohort Study.","authors":"Nicolás Tentoni, Ryan Combs, Miriam Hwang, Suzanne Ward, Andrea McCracken, Jennifer Lowe, Scott C Howard","doi":"10.3390/cancers16234050","DOIUrl":"https://doi.org/10.3390/cancers16234050","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to determine whether the occurrence of early-onset toxicities due to 5-fluorouracil (5-FU) in treatment-naive patients undergoing their first cycle of FOLFOX/FOLFIRINOX was associated with decreased overall survival, increased risk of treatment cessation, and hospitalization.</p><p><strong>Methods: </strong>This was a retrospective cohort study using patient information from community oncology practices. Patients who received their first dose of 5-FU from 1 January 2015 through 1 August 2023 were included. The occurrence of an early-onset 5-FU-related toxicity (during 5-FU infusion or up to 96 h after infusion completion) in the first cycle of FOLFOX/FOLFIRINOX was the explanatory variable. The primary endpoint was overall survival (OS); secondary endpoints included early treatment cessation and early hospital admission.</p><p><strong>Results: </strong>In total, 3988 patients were included; the median age was 62.9 years and 57.5% were male. Early-onset toxicities were observed in 19.1%, with vomiting, thrombocytopenia, and diarrhea being most common. Patients with early-onset toxicities had a median OS of 2.5 years [95% CI 2.2 to 2.9] compared with 5.3 years [95% CI 4.7 to 5.8] in patients without early-onset toxicities (<i>p</i> < 0.001). The occurrence of early-onset toxicities was associated with an adjusted hazard ratio of 1.61 [95% CI 1.44 to 1.80] and was also significantly associated with early treatment cessation (odds ratio [OR] 1.53, 95% CI 1.30 to 1.80) and early hospital admission (OR 8.69, 95% CI 3.45 to 24.18).</p><p><strong>Conclusions: </strong>Early-onset toxicities related to 5-FU during the first cycle of FOLFOX/FOLFIRINOX treatment were associated with poor outcomes. Early recognition and prompt intervention are pertinent to improve outcomes in patients receiving fluoropyrimidine chemotherapy.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Podoplanin (PDPN) in Advancing the Progression and Metastasis of Glioblastoma Multiforme (GBM).","authors":"Bharti Sharma, George Agriantonis, Zahra Shafaee, Kate Twelker, Navin D Bhatia, Zachary Kuschner, Monique Arnold, Aubrey Agcon, Jasmine Dave, Juan Mestre, Shalini Arora, Hima Ghanta, Jennifer Whittington","doi":"10.3390/cancers16234051","DOIUrl":"https://doi.org/10.3390/cancers16234051","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a malignant primary brain tumor categorized as a Grade 4 astrocytic glioma by the World Health Organization (WHO). Some of the established risk factors of GBM include inherited genetic syndromes, body mass index, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and therapeutic ionizing radiation. Vascular anomalies, including local and peripheral thrombosis, are common features of GBM. Podoplanin (PDPN), a ligand of the C-type lectin receptor (CLEC-2), promotes platelet activation, aggregation, venous thromboembolism (VTE), lymphatic vessel formation, and tumor metastasis in GBM patients. It is regulated by Prox1 and is expressed in developing and adult mammalian brains. It was initially identified on lymphatic endothelial cells (LECs) as the E11 antigen and on fibroblastic reticular cells (FRCs) of lymphoid organs and thymic epithelial cells as gp38. In recent research studies, its expression has been linked with prognosis in GBM. PDPN-expressing cancer cells are highly pernicious, with a mutant aptitude to form stem cells. Such cells, on colocalization to the surrounding tissues, transition from epithelial to mesenchymal cells, contributing to the malignant carcinogenesis of GBM. PDPN can be used as an independent prognostic factor in GBM, and this review provides strong preclinical and clinical evidence supporting these claims.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carcinoembryonic Antigen Expression in Human Tumors: A Tissue Microarray Study on 13,725 Tumors.","authors":"Kristina Jansen, Lara Kornfeld, Maximilian Lennartz, Sebastian Dwertmann Rico, Simon Kind, Viktor Reiswich, Florian Viehweger, Ahmed Abdulwahab Bawahab, Christoph Fraune, Natalia Gorbokon, Andreas M Luebke, Claudia Hube-Magg, Anne Menz, Ria Uhlig, Till Krech, Andrea Hinsch, Frank Jacobsen, Eike Burandt, Guido Sauter, Ronald Simon, Martina Kluth, Stefan Steurer, Andreas H Marx, Till S Clauditz, David Dum, Patrick Lebok, Sarah Minner, Christian Bernreuther","doi":"10.3390/cancers16234052","DOIUrl":"https://doi.org/10.3390/cancers16234052","url":null,"abstract":"<p><strong>Background/objectives: </strong>Carcinoembryonic antigen (CEA) is a cell-surface glycoprotein serving as a drug target, diagnostic marker, and serum marker for cancer monitoring. However, prevalence data on CEA expression in cancer tissues vary considerably. This study was designed to determine CEA expression in normal and neoplastic tissues.</p><p><strong>Methods: </strong>A tissue microarray containing 13,725 samples from 120 different tumor types, as well as 76 different normal tissue types, was analyzed by immunohistochemistry (IHC).</p><p><strong>Results: </strong>CEA was detectable in 65 (54.2%) of 120 tumor categories, including 49 (40.8%) tumor types with at least one strongly positive case. CEA positivity was most common in colorectal adenomas (100%) and carcinomas (98.7%), other gastrointestinal adenocarcinomas (61.1-80.3%), medullary carcinomas of the thyroid (96.3%), pulmonary adenocarcinoma (73.7%), mucinous carcinomas of the ovary (79.8%) and the breast (43.2%), small-cell carcinomas of the lung (64.3%), and urinary bladder (38.9%). CEA overexpression was linked to high tumor grade and invasive growth (<i>p</i> < 0.0001 each) in urinary bladder cancer, and estrogen and HER2 receptor positivity (<i>p</i> ≤ 0.0158) in invasive breast cancer of no special type. In colorectal adenocarcinomas, reduced CEA expression was associated with mismatch repair deficiency (<i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"16 23","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}