Endocrine-related cancer最新文献

Reappraisal of BRAFK601E-positive thyroid tumors in the NIFTP era. 在 NIFTP 时代重新评估 BRAFK601E 阳性甲状腺肿瘤。

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0207

William Reed Doerfler, Alyaksandr V Nikitski, Shannon Keating, Daniel Spagnolo, Cihan Kaya, Elena Morariu, Esra Karslioglu French, Linwah Yip, Marina N Nikiforova, Abigail I Wald, Yuri E Nikiforov

{"title":"Reappraisal of BRAFK601E-positive thyroid tumors in the NIFTP era.","authors":"William Reed Doerfler, Alyaksandr V Nikitski, Shannon Keating, Daniel Spagnolo, Cihan Kaya, Elena Morariu, Esra Karslioglu French, Linwah Yip, Marina N Nikiforova, Abigail I Wald, Yuri E Nikiforov","doi":"10.1530/ERC-24-0207","DOIUrl":"https://doi.org/10.1530/ERC-24-0207","url":null,"abstract":"BRAFK601E is an uncommon mutation typically found in encapsulated follicular-patterned thyroid tumors. Previous studies on BRAFK601E-positive thyroid tumors were conducted before implementation of the non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP) diagnosis. This study aimed to characterize BRAFK601E-positive tumors and evaluate changes in diagnosis and management of these patients after introduction of NIFTP. We evaluated 25 thyroid tumors that were positive for BRAFK601E and diagnosed considering the NIFTP criteria. Clinicopathologic characteristics and recurrence rates of these tumors were compared to 29 BRAFK601E-positive tumors diagnosed prior to the acceptance of NIFTP diagnosis. RNA-seq analysis was performed on 10 BRAFK601E-positive tumors. In the current study, 72% of BRAFK601E-positive tumors were diagnosed as non-invasive tumors on resection, with NIFTP (48% of all tumors) being the most common diagnosis. BRAFK601E-positive tumors exhibited a RAS-like gene expression profile with BRAF-RAS score (BRS) and thyroid differentiation score (TDS) distinct from BRAFV600E-positive tumors (P<0.001). Since 2016, patients with BRAFK601E-positive tumors less frequently underwent total thyroidectomy (41% vs 100%, P<0.001) and received radioiodine (7% vs 75%, P<0.001). None of the tumors positive for an isolated BRAFK601E mutation from the current or 2016 studies showed recurrences on follow-up. Our study demonstrates that most BRAFK601E-positive tumors are low risk, RAS-like tumors, which were diagnosed as NIFTP in half of all study cases. Since 2016, patients with BRAFK601E-positive nodules receive less aggressive treatment. The risk of recurrence of BRAFK601E-positive tumors without other, high-risk features appears to be low, and lobectomy without radioiodine is likely sufficient treatment for these patients.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484033","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}

引用次数: 0

The complex landscape of luminal breast cancer. 腔隙性乳腺癌的复杂情况。

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0201

Catrin Lutz, Hendrik A Messal, Damir Vareslija, Stefan Prekovic

引用次数: 0

Cellular Mechanisms of RET Receptor Dysfunction in Multiple Endocrine Neoplasia 2. 多发性内分泌肿瘤中 RET 受体功能障碍的细胞机制 2.

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0187

Timothy J Walker, Lois M Mulligan

{"title":"Cellular Mechanisms of RET Receptor Dysfunction in Multiple Endocrine Neoplasia 2.","authors":"Timothy J Walker, Lois M Mulligan","doi":"10.1530/ERC-24-0187","DOIUrl":"https://doi.org/10.1530/ERC-24-0187","url":null,"abstract":"REarranged during Transfection (RET) is a developmentally important receptor tyrosine kinase that has been identified as an oncogenic driver in a number of cancers. Activating RET point-mutations give rise to the inherited cancer syndrome Multiple Endocrine Neoplasia type 2 (MEN2), characterized by medullary thyroid carcinoma. There are two MEN2 subtypes, MEN2A and MEN2B, that differ in tumour aggressiveness and the associated constellation of other disease features, which are caused by distinct patterns of RET amino acid substitution mutations. MEN2A-RET mutations affecting extracellular cysteine residues promote ligand independent dimerization and constitutive RET activity, while MEN2B is caused by a single amino acid change in the tyrosine kinase domain of RET, releasing autoinhibition and producing a more active MEN2B-RET kinase that can promote signalling as monomers or dimers in the absence of ligand. These mutations cause intrinsic biochemical changes in RET structure and activation but also trigger extrinsic effects that alter RET cellular location, interactions and mechanisms of downregulation that can prolong or mislocate RET activity, changing or enhancing functional outcomes. Together, changes in specific combinations of RET-mediated effects associated with different mutations give rise to the distinct MEN2 disease phenotypes. Here, we discuss the current understanding of the intrinsic and extrinsic characteristics of RET MEN2A cysteine and MEN2B mutants and how these contribute to transforming cellular processes and to differences in tumour progression and disease aggressiveness.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515228","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}

引用次数: 0

Chromosomal Alteration Patterns in PitNETs: Massive Losses in Aggressive Tumors. PitNETs 的染色体畸变模式：侵袭性肿瘤中的大量缺失

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0070

Maaia Margo Jentus, Leontine Bakker, Marco Verstegen, Iris Pelsma, Tom van Wezel, Dina Ruano, Ellen Kapiteijn, Stijn Crobach, Nienke R Biermasz, Hans Morreau

{"title":"Chromosomal Alteration Patterns in PitNETs: Massive Losses in Aggressive Tumors.","authors":"Maaia Margo Jentus, Leontine Bakker, Marco Verstegen, Iris Pelsma, Tom van Wezel, Dina Ruano, Ellen Kapiteijn, Stijn Crobach, Nienke R Biermasz, Hans Morreau","doi":"10.1530/ERC-24-0070","DOIUrl":"https://doi.org/10.1530/ERC-24-0070","url":null,"abstract":"The molecular biology of pituitary neuroendocrine tumors (PitNETs) revealed few recurrent mutations and extensive chromosomal alterations, with the latter being the driving force in a subset of these lesions. Addressing the need for an easily applicable diagnostic tool, we conducted a retrospective study of 61 PitNETs operated at a tertiary care center. All cases were subtyped according to the 2022 WHO classification of endocrine tumors. A genome wide NGS panel targeting 1500 single-nucleotide polymorphisms (SNP) was used to classify chromosomal imbalances, loss of heterozygosity and copy number variations in DNA from formalin fixed paraffin embedded tissues. We identified four distinct chromosomal patterns, with varying distribution among different tumor lineages. Forty-two of 61 (69%) PitNETs showed chromosomal alterations. Gonadotroph PitNETs showed mostly quiet genomes. The majority of lactotroph PitNETs (19/20, 95%) were altered, exhibiting a gained genome and a remarkably low recurrence rate. Nine of ten (90%) corticotroph PitNETs harbored chromosomal alterations, of which two aggressive corticotroph tumors and one metastatic corticotroph PitNET showed massive chromosomal losses leading to near haploid/near homozygous genomes. The comparison of the molecular profile of primary and recurrent PitNETs of five patients showed no significant accumulation of alterations over time. A simple genome wide 1500 SNP test can be used in the identification of outspoken aggressive subsets of PitNET by the occurrence of a near haploid/near homozygous genome. Furthermore, the presence of neoplastic tissue in resected material can be potentially confirmed for non-gonadotroph PitNETs in suboptimal histological assessment conditions.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515229","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}

引用次数: 0

Genotype/phenotype correlations in multiple endocrine neoplasia type 2. 多发性内分泌肿瘤 2 型的基因型/表型相关性。

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0139

Frederic Castinetti, Charis Eng

{"title":"Genotype/phenotype correlations in multiple endocrine neoplasia type 2.","authors":"Frederic Castinetti, Charis Eng","doi":"10.1530/ERC-24-0139","DOIUrl":"https://doi.org/10.1530/ERC-24-0139","url":null,"abstract":"Multiple endocrine neoplasia type 2 (MEN 2) is a rare hereditary endocrine tumour syndrome caused by mutations in the rearranged during transfection (RET) gene. MEN 2 is divided into two main entities, MEN 2A and MEN2B, both of which present with medullary thyroid cancer (MTC) in approximately 100% of cases and pheochromocytoma in 50% of cases. Specific RET mutations are associated with a risk of early onset of MTC, from 1 year of age (highest risk) to 5 years of age (high risk). This risk defines the optimal timing for thyroidectomy, ideally at an age when the disease has not spread. This is the most important genotype-phenotype correlation observed in MEN 2. Specific RET mutations also define the penetrance of pheochromocytoma. However, despite the presence of these highest/high risk variants, some patients unexpectedly present with non-aggressive MTC or never present with pheochromocytoma, suggesting that factors other than the major RET variant may modify the natural history and genotype-phenotype correlations. Improving our understanding of the genotype-phenotype correlations would allow individualizing the management and follow-up of patients with MEN 2. The aim of this brief review is to discuss the main genotype-phenotype correlations in MEN 2 and the potential factors that might influence these correlations.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484031","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}

引用次数: 0

Living with a RET gene mutation: patient perspectives. 与 RET 基因突变共存：患者的观点。

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0130

Caroline Brain, Joanna Grey, Kirstie Purnell

{"title":"Living with a RET gene mutation: patient perspectives.","authors":"Caroline Brain, Joanna Grey, Kirstie Purnell","doi":"10.1530/ERC-24-0130","DOIUrl":"https://doi.org/10.1530/ERC-24-0130","url":null,"abstract":"Multiple endocrine neoplasia type 2 (MEN2) is the collective term for 2 distinct types of autosomal dominantly inherited neuroendocrine neoplasm (NEN) syndromes (Barakat, 2004); MEN2A and MEN 2B (or MEN3). MEN2 is characterised by medullary thyroid cancer (99%) and phaeochromocytoma (50%) but also other conditions according to specific genotype. MEN2A also includes a 25% risk of developing parathyroid hyperplasia and is now recognised as 4 separate syndromes: Classic MEN2A, MEN2A with cutaneous lichen amyloidosis (CLA), MEN2A with Hirschsprung's disease (HD) and Familial MTC (Wells, 2015). MEN2B accounts for around 5% of all MEN2 cases and predisposes patients to diffuse intestinal ganglioneuromatosis (Goncharova, 2020), mucosal neuromas, and musculoskeletal abnormalities (Henderson, 2022). MEN2 is autosomal dominantly inherited meaning that several generations in a single family may be affected by the same syndrome. We present a mini review of 4 case studies (x2 MEN2A, x2 MEN2B) that illustrate the advantages of RET testing, as well as some of the likely obstacles that must be overcome to receive a diagnosis of MEN2A or MEN2B. In addition, despite improved genotype/phenotype correlation in MEN2, we highlight that not all cases are 'typical' which emphasises the need for all MEN2 patients to be cared for in a centre of expertise and experience. Some of our case study patients or parents also took this opportunity to personally tell us more about their lives with MEN2, illustrating the need for more research into the psychosocial impact of these hereditary diseases.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549666","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}

引用次数: 0

Mechanisms of RET mediated signal transduction. RET 介导的信号转导机制。

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0131

Francesca Carlomagno, Marialuisa Moccia, Giorgia Federico, Massimo Santoro

引用次数: 0

AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma. AGO2 蛋白：作为肾上腺皮质癌新型生物标志物的 miRNA 通路中的一个关键酶。

Endocrine-related cancer Pub Date : 2024-10-01 DOI: 10.1530/ERC-24-0061

Anila Hashmi, Alexander Papachristos, Stan B Sidhu, Gyorgy Hutvagner

{"title":"AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma.","authors":"Anila Hashmi, Alexander Papachristos, Stan B Sidhu, Gyorgy Hutvagner","doi":"10.1530/ERC-24-0061","DOIUrl":"https://doi.org/10.1530/ERC-24-0061","url":null,"abstract":"Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy characterised by diagnostic challenges, high recurrence rates, and poor prognosis. This study explored the role microRNA (miRNA) processing genes in ACC, and their potential role as diagnostic and prognostic biomarkers. We analysed the mRNA expression levels of miRNA machinery components (DROSHA, DGCR8, XPO5, RAN, DICER, TARBP2 and AGO2) utilising mRNA-Seq data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) projects. Additionally, protein levels were quantified in tissue samples from the Kolling Institute of Medical Research's tumour bank. Our results demonstrated that among all miRNA processing components, AGO2 exhibited significant overexpression in ACC compared to the normal adrenal cortex (NAC) and benign adrenal adenoma (AA) (p < 0.001). Kaplan-Meier survival analysis indicated that higher AGO2 expression correlated with significantly worse overall survival in ACC patients (HR 7.07, p < 0.001). Among 32 cancer types in TCGA, the prognostic significance of AGO2 was most prominent in ACC. This study is the first to report AGO2's potential as a diagnostic and prognostic biomarker in ACC, emphasising its significance in ACC pathogenesis and potential application as a non-invasive liquid biopsy biomarker.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484030","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}

引用次数: 0

Management of advanced high grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): comprehensive review of the current literature. 晚期高级别胃肠胰神经内分泌肿瘤（GEP-NENs）的治疗：现有文献综述。

Endocrine-related cancer Pub Date : 2024-09-21 Print Date: 2024-10-01 DOI: 10.1530/ERC-24-0025

A Mohamed, M Trybula, S L Asa, T R Halfdanarson, M B Sonbol

{"title":"Management of advanced high grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): comprehensive review of the current literature.","authors":"A Mohamed, M Trybula, S L Asa, T R Halfdanarson, M B Sonbol","doi":"10.1530/ERC-24-0025","DOIUrl":"10.1530/ERC-24-0025","url":null,"abstract":"The classification and management of neuroendocrine neoplasms (NENs) arising in the tubular gastrointestinal (GI) tract and pancreas have significantly evolved over the last decades. In the latest WHO classification published in 2022, NENs are separated regardless of their primary origin into two main groups: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The substantial changes in the grading system changed the definition of grade 3 to include high-grade well-differentiated NETs (G3-NETs), and poorly differentiated NECs (-NECs). Although these two subgroups are considered high grades with Ki-67 >20%, they have different genomic profiles, prognosis, and clinical behavior, which critically influence their treatment strategies. The available clinical trial data to guide therapy of these high-grade subgroups are extremely limited, which impacts their management. In this review, we will summarize the current advances in the multidisciplinary approach for the management of high-grade gastroenteropancreatic NENs (GEP-NENs) including G3-NETs and NECs.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918391","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}

引用次数: 0

Endocrine-related cancer Pub Date : 2024-09-21 Print Date: 2024-10-01 DOI: 10.1530/ERC-24-0111

Adam I Kaplan, Trisha Dwight, Catherine Luxford, Diana E Benn, Roderick J Clifton-Bligh

{"title":"SDHA-related phaeochromocytoma and paraganglioma: review and clinical management.","authors":"Adam I Kaplan, Trisha Dwight, Catherine Luxford, Diana E Benn, Roderick J Clifton-Bligh","doi":"10.1530/ERC-24-0111","DOIUrl":"10.1530/ERC-24-0111","url":null,"abstract":"Phaeochromocytomas and paragangliomas (collectively termed PPGL) are rare yet highly heritable neuroendocrine tumours, with over one-third of cases associated with germline pathogenic variants (PVs) in numerous genes. PVs in the succinate dehydrogenase subunit-A gene (SDHA) were initially implicated in hereditary PPGL in 2010, and SDHA has since become an important susceptibility gene accounting for up to 2.8% of cases. However, it remains poorly understood, particularly regarding the clinical nature of SDHA PPGL, rates of recurrence and metastasis, and the nature of metastatic disease. We present a narrative review of SDHA-related PPGL, covering pathophysiology, relevance to current clinical practice, and considerations for clinical genetics. We analyse a pool of 107 previously reported cases of SDHA-associated PPGL to highlight the spectrum of SDHA-related PPGL. Our analysis demonstrates that SDHA PPGL occurs across a wide age range (11-81 years) and affects men and women equally. SDHA PPGL typically presents as single tumours (91%), usually occurring in the head and neck (46%) or abdomen (43%, including 15% with phaeochromocytomas). Metastatic disease was reported in 25.5% of cases, with bone (82%) and lymph nodes (71%) being the most common sites of metastasis, often identified many years after the initial diagnosis. A family history of SDHA-related neoplasia was rare, reported in only 4% of cases. Understanding the clinical nature and risks associated with SDHA PVs is essential for facilitating the optimal management of patients and their families.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918392","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}

引用次数: 0