Endocrine-related cancer最新文献

{"title":"Distinct molecular profiles of indeterminate and malignant thyroid nodules in patients under 21 years of age.","authors":"Julio C Ricarte-Filho, Luz Castellanos, Steven G Waguespack, Julian Bryan, Mohammed Alshalalfa, Taylor B Cavazos, Yang Chen, Andrew Bauer, Joshua P Klopper, Richard T Kloos, Aime T Franco","doi":"10.1530/ERC-26-0115","DOIUrl":"10.1530/ERC-26-0115","url":null,"abstract":"<p><p>Although uncommon, thyroid nodules (TNs) in pediatric and young adult patients carry a higher malignancy risk and often present with a high burden of metastatic disease than in adults. The molecular features underlying this distinct clinical behavior remain unclear. We analyzed Afirma Genomic Sequencing Classifier (GSC) data from 283,621 TNs, comparing patients <21 and ≥21 years old. Cytology (Bethesda), GSC benign (B) vs suspicious (S) calls, and Afirma Xpression Atlas (XA) variant/fusion profiles were evaluated in GSC-S and Bethesda V/VI samples. Genome-wide expression was used to derive pathway signatures and thyroid cancer-related scores: BRAF-RAS score (BRS), ERK signaling score, follicular-to-mesenchymal transition (FMT) score, epithelial-to-mesenchymal transition (EMT) score, and thyroid differentiation score (TDS). Among 2,397 patients <21 years (median age: 18.9; 81.4% female) and 281,224 adults ≥21 years (median age: 59.8; 77.1% female), the <21-year samples showed more Bethesda V/VI cytology (14.5% vs 5.0%; P < 0.0001) and a lower GSC-B rate (43.5% vs 68.8%; P < 0.0001). In GSC-S samples, total variant detection was higher in the <21-year group (45.3% vs 37.4%), with enriched BRAF p.V600E, TSHR, and DICER1 variants, while HRAS variants were more common in adults (all P < 0.01). Gene fusions involving RET, NTRK3, and ALK were enriched in the <21-year group (14.5% vs 5.5%; P < 0.0001). TERT promoter mutations were absent in <21-year GSC-S and Bethesda V/VI samples (vs 4.2% and 9.3% in adults). The GSC-S <21-year cohort showed cell-cycle pathway enrichment. The RET/NTRK/ALK-positive <21-year group demonstrated enrichment of angiogenesis and EMT pathways, higher ERK/EMT/FMT scores, and lower BRS/TDS vs genotyped-matched adults. These molecular differences provide mechanistic insight into the more invasive phenotype in pediatric and young adult TNs.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPGLomics: an interactive platform for pheochromocytoma and paraganglioma transcriptomics.","authors":"Hussam Alkaissi, Catherine M Gordon, Karel Pacak","doi":"10.1530/ERC-26-0140","DOIUrl":"10.1530/ERC-26-0140","url":null,"abstract":"<p><p>Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with unique biological behavior and remarkably high heritability, yet dedicated bioinformatics resources for these diagnoses remain limited. Existing cancer multi-omics platforms are pan-cancer in scope, often lacking the disease-specific annotations, granularity, and cross-database harmonization required for meaningful stratification and hypothesis generation. Here, we introduce PPGLomics, an interactive Web-based platform designed for comprehensive PPGL transcriptomics analysis. PPGLomics v1.0 integrates two major datasets, the TCGA-PCPG cohort (n = 160) spanning multiple molecular subtypes and the A5 Consortium SDHB cohort (n = 91) with detailed clinicopathological and molecular annotations. The platform provides basic and clinical scientists, as well as a broad range of healthcare professionals, with tools for differential expression analysis, correlation analysis, survival analysis, and visualization, including boxplots, heatmaps, volcano plots, and Kaplan-Meier survival plots, enabling exploration of gene expression patterns across PPGL subtypes without requiring bioinformatics expertise. PPGLomics v1.0 is freely available at https://alkaissilab.shinyapps.io/PPGLomics.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic, cellular, and environmental factors influencing tumourigenesis in carriers of succinate dehydrogenase germline mutations.","authors":"Eugenie S Lim, Jean-Pierre Bayley, Anne-Paule Gimenez-Roqueplo, Roderick J Clifton-Bligh, Susan Richter","doi":"10.1530/ERC-26-0282","DOIUrl":"10.1530/ERC-26-0282","url":null,"abstract":"<p><p>Succinate dehydrogenase (SDH) is an enzyme complex that plays a major role in cellular metabolism, as it sits at the interface between carbon metabolism in the Krebs cycle and oxidative phosphorylation for energy production. The precursor and product of the enzymatic reaction, succinate and fumarate, respectively, are regulators of various cellular and biological processes, such as epigenetic status, hypoxia responses and angiogenesis, metabolic reprogramming, tumourigenesis, and immune responses. Succinate is considered an oncometabolite, and SDHx genes are tumour suppressor genes. Carriers of germline pathogenic variants (PVs) in one of the SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2) carry a life-long risk of developing tumours, predominantly phaeochromocytomas and paragangliomas (PPGLs). Research has focused mainly on the disease state in which, in accordance with the Knudson two-hit model, the second allele is inactivated in tumour cells; the biological consequences are massive intracellular accumulation of succinate and/or reactive oxygen species (ROS), which in turn leads to tumourigenesis. Little is known about the haploinsufficient state, in which the wild-type SDHx copy at least partially sustains SDH function and keeps intracellular succinate and ROS levels in ranges that are, if not normal, then at least non-tumourigenic. This review will consolidate the literature regarding genotype differences between SDHx PV carriers, the phenotype of non-tumoural cells in healthy individuals, and the role of environmental factors in influencing tumour development, potentially via tipping succinate (or ROS) levels above a tumourigenic threshold.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour-infiltrating lymphocytes differ across MammaPrint® classifications in breast cancer.","authors":"Carmen Ariño-Palao, Irene Carretero-Barrio, Sara Martos-Meléndez, Tamara Caniego-Casas, Marta Rosas, Noelia Martínez-Jañez, María Fernández-Abad, María Concepción Sánchez, Teresa Presa-Abos, Javier Zamora, Juan Martínez-Aedo Castro, María J Ledesma-Carbayo, José Palacios, Belén Pérez-Mies","doi":"10.1530/ERC-26-0116","DOIUrl":"10.1530/ERC-26-0116","url":null,"abstract":"<p><p>MammaPrint® refines risk stratification in early oestrogen receptor-positive, HER2-negative breast cancer, evolving from a binary to a four-tier classification (UltraLow-Risk, Low-Risk, High-Risk 1, and High-Risk 2). The relationship between routine histopathological features, immune infiltration, and genomic risk within this framework remains incompletely characterized in luminal disease. We retrospectively analysed 492 luminal breast carcinomas with available MammaPrint® results. Clinicopathological variables (including histological subtype, grade, Ki-67, hormone receptor expression, lymphovascular invasion (LVI), and HER2-low status) were recorded. Stromal tumour-infiltrating lymphocytes (TILs) were quantified according to the criteria of Salgado et al. and spatially categorized as immune-deserted, stromal-restricted, immune-excluded, or inflamed patterns. CD4 and CD8 infiltration was assessed by immunohistochemistry on tissue microarrays. Associations with binary and four-tier MammaPrint® categories were examined using multivariable models. High-Risk tumours (41%) were enriched for increased grade, Ki-67, and LVI and lower PR expression. In High-Risk tumours, inflamed spatial patterns were more frequent and median TIL levels were significantly higher compared with Low-Risk tumours (15% vs 5%, P < 0.001). CD4 and CD8 infiltration increased with genomic risk, and CD4 retained a modest but statistically significant association after adjustment for conventional pathological variables. In the four-tier model, UltraLow-Risk/Low-Risk tumours showed minimal TILs and were enriched for invasive lobular carcinoma, whereas High-Risk 1/High-Risk 2 tumours displayed progressively higher proliferative and immune features. No association was observed between HER2-low status and genomic risk. Immune infiltration parallels proliferative and genomic risk gradients in luminal breast cancer. These findings indicate that immune descriptors align with the genomic risk continuum, although their independent prognostic contribution beyond established genomic assays requires further evaluation.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding pheochromocytomas and paragangliomas PET phenotypes: looking beyond genotype.","authors":"Alessio Imperiale, Valentina Berti, Philippe Baltzinger, David Taieb","doi":"10.1530/ERC-26-0340","DOIUrl":"10.1530/ERC-26-0340","url":null,"abstract":"","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging insights into the pathophysiology of pituitary tumour microenvironment.","authors":"Antonio C Fuentes-Fayos, Ignacio Gil-Duque, Ana S De la Rosa-Herencia, André Sarmento-Cabral, Álvaro Flores-Martínez, David A Cano, Antonio J Martínez-Fuentes, Raúl M Luque","doi":"10.1530/ERC-26-0262","DOIUrl":"10.1530/ERC-26-0262","url":null,"abstract":"<p><p>Pituitary tumours (PiTs) are a heterogeneous group of diseases of the anterior pituitary gland. While they are often described as rare diseases, the actual prevalence of these tumours is higher than commonly believed, accounting for at least 15% of all intracranial tumours. Yet, the high heterogeneity of the different PiTs (intra- and inter-patient heterogeneity), rooted in part in the intrinsic cellular diversity of the normal pituitary gland itself, has significantly limited the understanding of the biological mechanisms linked to their development, progression and aggressive behaviour. Like other cancer types, understanding the tumour microenvironment (TME) might help to better understand the pathophysiology of PiT cells beyond genetics, epigenetics, transcriptomics and proteomics and could constitute a personalized approach to dealing with these complex and heterogeneous endocrine-related tumours and to developing novel diagnostic, prognostic and future therapeutic tools. Importantly, the concept of TME relies on the notion that tumours are more than a group of tumour cells, but rather a heterogeneous mixture of tumour and non-tumour cells interacting with local components (growth factors, cytokines, etc.) within a remodelled tumour extracellular matrix (ECM). In this review, we will focus on describing the latest research on this complex TME-PiTs architecture network, which could bring a new era in diagnosing and treating these heterogeneous and complex endocrine-related cancers.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSIP1::TBL1X: a recurrent gene fusion in pancreatic neuroendocrine tumors.","authors":"Daniel Ackerman, Elisabeth R Seyferth, Wuyan Li, Julia E Youngman, Jelsia N Cottone, Cecilia A Wright, Robyn T Sussman, Abashai A Woodard, David C Metz, Bryson W Katona, Michael C Soulen, Daniel M DePietro, Jennifer R Eads, Terence P Gade","doi":"10.1530/ERC-26-0177","DOIUrl":"10.1530/ERC-26-0177","url":null,"abstract":"<p><p>Effective treatment of metastatic neuroendocrine tumors (NETs) is limited by a lack of targeted therapies and clinically useful predictive biomarkers. We applied complementary genomic profiling technologies, including optical genome mapping (OGM) and whole exome sequencing (WES), to 70 liver metastases of NETs from multiple anatomical primary sites to identify actionable genomic alterations. We detected recurrent fusions involving TBL1X (PSIP1::TBL1X) and BEND2 (CHD7::BEND2 and NEO1::BEND2) by OGM in pancreatic neuroendocrine tumors (pNETs). The expression of the PSIP1::TBL1X fusion was confirmed by PacBio Iso-Seq long-read transcriptome sequencing and nested rtPCR, and fusion protein expression was established by western blotting. Expression of the PSIP1::TBL1X fusion was also assayed in a separate cohort of 31 specimens from 28 pNET cases by rtPCR. Across both cohorts, PSIP1::TBL1X was identified in 11% of pNET patients with available metastatic tissue, but was not detected in primary tumor specimens. All PSIP1::TBL1X fusion isoforms were found to retain early exons of PSIP1 and the complete coding sequence of TBL1X. Consistent with prior reports, BEND2 fusions were associated with high-grade tumors and may represent a clinically useful biomarker for aggressive disease. Notably, TBL1X and BEND2 fusions did not co-occur with ATRX/DAXX mutations, defining a distinct molecular subgroup of pNETs. This study highlights the importance of structural variant profiling in molecular profiling studies and supports a revised view of the role of gene fusions in neuroendocrine malignancies.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between PD-1/PD-L1 expression and clinicopathological parameters as well as prognosis in neuroendocrine neoplasms of the digestive system: a systematic review and meta-analysis.","authors":"Qiming Zheng, Xinyue Xie, Qingjun Guo, Chiyi Chen, Wentao Jiang","doi":"10.1530/ERC-26-0145","DOIUrl":"10.1530/ERC-26-0145","url":null,"abstract":"<p><p>Neuroendocrine neoplasms (NENs) are a highly heterogeneous group of tumors originating from the neuroendocrine system, predominantly occurring in the gastrointestinal tract and lungs. This meta-analysis aimed to clarify the association of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression with clinicopathological parameters and prognosis in patients with digestive system NENs. A systematic literature search was performed in PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Biomedical Literature Database (CBM) from each database's inception to February 2026. Eligible studies were analyzed using Stata 17.0 software, with 29 studies including 2,633 patients. Results showed no significant association between PD-1 expression and clinicopathological parameters or prognosis. In contrast, PD-L1 expression was closely correlated with high tumor grade (OR = 2.73, 95% CI: 1.33-5.60, P = 0.006) and pancreatic primary tumor site (OR = 2.58, 95% CI: 1.21-5.52, P = 0.014). Regarding prognosis, positive PD-L1 expression was associated with inferior overall survival (OS) in gastroenteropancreatic NENs (GEP-NENs) (HR = 1.77, 95% CI: 1.25-2.51, P = 0.001) but favorable OS in esophageal NENs (HR = 0.60, 95% CI: 0.37-0.99, P = 0.047). In conclusion, PD-L1 expression correlates with high tumor grade and pancreatic origin. It serves as a predictive biomarker for poor OS in GEP-NENs but favorable prognosis in esophageal NENs, highlighting the divergent prognostic value of the PD-1/PD-L1 axis across digestive system NEN subtypes. These findings provide hypothesis-generating evidence for the potential rationale of immune checkpoint inhibitors in high-grade or poorly differentiated GEP-NENs, although their clinical application requires further prospective validation.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonism in prostate cancer: insights and perspectives.","authors":"Sandro La Vignera, Rosita A Condorelli","doi":"10.1530/ERC-26-0398","DOIUrl":"10.1530/ERC-26-0398","url":null,"abstract":"","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo CRISPR screening links NFKB1 to endocrine resistance in ER+ breast cancer.","authors":"Cancan Lyu, Samuel D Hall, Mark A Stamnes, Songhai Chen","doi":"10.1530/ERC-25-0463","DOIUrl":"10.1530/ERC-25-0463","url":null,"abstract":"<p><p>Resistance to endocrine therapy (ET) remains a major clinical challenge in the treatment of estrogen receptor-positive (ER+) breast cancer, underscoring the need for novel therapeutic targets. To identify genetic drivers of ET resistance, we conducted an in vivo genome-wide CRISPR-Cas9 screen in MCF7 cells implanted into ovariectomized nude mice under estrogen-deprived conditions. Despite the bottlenecks inherent to in vivo pooled screening, recurrent enrichment analysis identified NFKB1 as a candidate regulator of estrogen-independent tumor progression. Functional studies confirmed that NFKB1 deficiency enhanced tumorigenicity and conferred resistance to tamoxifen and fulvestrant both in vitro and in vivo. Mechanistically, transcriptomic and biochemical analyses revealed that NFKB1 deficiency activated canonical NF-κB signaling, leading to inflammatory gene induction and enhanced ER signaling. Furthermore, pharmacologic inhibition of NF-κB signaling restored ET sensitivity in NFKB1-deficient cells. Analysis of TCGA breast cancer datasets revealed reduced NFKB1 expression in luminal breast tumors, whereas expression of other NF-κB family members was largely unchanged. Further analysis showed that low NFKB1 expression was associated with poorer clinical outcomes in patients with ER+ breast cancer. Collectively, these findings identify NFKB1 as a negative regulator of NF-κB signaling and endocrine resistance in ER+ breast cancer and provide mechanistic evidence linking NF-κB activation to ligand-independent ER signaling. Our results support further investigation of NFKB1 as a candidate biomarker and of NF-κB pathway inhibition as a potential therapeutic strategy in endocrine therapy-resistant breast cancer. These findings also illustrate the utility of in vivo CRISPR screening for identifying candidate regulators of endocrine resistance in breast cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}