Endocrine-related cancer最新文献_第3页

Integrin-fibronectin interaction is a pivotal biological and clinical determinant in papillary thyroid carcinoma. 整合素-纤维连接蛋白相互作用是甲状腺乳头状癌的关键生物学和临床决定因素。

Endocrine-related cancer Pub Date : 2025-06-05 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0101

Domenico Rocco, Anna Tortora, Vincenzo Marotta, Aline Maria Machado, Heloisa S Selistre-de-Araújo, Mario Vitale

{"title":"Integrin-fibronectin interaction is a pivotal biological and clinical determinant in papillary thyroid carcinoma.","authors":"Domenico Rocco, Anna Tortora, Vincenzo Marotta, Aline Maria Machado, Heloisa S Selistre-de-Araújo, Mario Vitale","doi":"10.1530/ERC-25-0101","DOIUrl":"10.1530/ERC-25-0101","url":null,"abstract":"Integrins influence tumor growth, metastasis, and angiogenesis, making them potential targets for therapeutic intervention. In this study, we analyzed the TCGA mRNA-seq dataset to assess the expression levels of fibronectin (FN1) and associated integrin subunits, evaluating their relationship with clinical features in papillary thyroid cancer (PTC). These findings were further validated in a cell model. FN1 mRNA levels in BRAFV600E-positive PTC were 80-fold compared to normal thyroid tissue (NT), whereas PTC with RAS mutations exhibited FN1 levels similar to NT. ITGAV, encoding the αv integrin subunit, which pairs with β3 to form a receptor for FN, was also overexpressed in PTC. Elevated FN1 expression, and to a lesser extent ITGAV, correlated positively with lymph node metastasis, advanced cancer stages, extrathyroidal extension, and poorer prognoses. Patients in the highest quartile of FN1 expression had an increased risk of disease recurrence (OR = 7.277, 95% CI: 2.019-26.191, P < 0.0024). A non-tumoral thyroid cell line and two PTC cell lines were used as models to validate the mRNA-seq results. The proliferation and migration of a FN1 knock-out PTC cell mutant were significantly reduced and proliferation was restored upon the addition of soluble FN. DisBa-01, a recombinant RGD-disintegrin derived from Bothrops alternatus snake venom, which acts as an antagonist to the FN/αvβ3 interaction, inhibited PTC cell proliferation and migration. These results demonstrate that FN expression is a hallmark of aggressiveness in PTC. FN/αvβ3 interaction plays a pivotal role in PTC, suggesting that the FN/αvβ3 signaling is a potential therapeutic target for disintegrins or other molecules with similar action.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153037","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

Oxygen regulates proliferation and phenotype in the RS0 SDH-deficient pheochromocytoma cell line. 氧调节RS0 sdh缺陷嗜铬细胞瘤细胞系的增殖和表型。

Endocrine-related cancer Pub Date : 2025-06-03 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0022

James F Powers, Brent Cochran, James D Baleja, Inna Lomakin, Xue Zhang, Annette Shepard-Barry, Arthur S Tischler

{"title":"Oxygen regulates proliferation and phenotype in the RS0 SDH-deficient pheochromocytoma cell line.","authors":"James F Powers, Brent Cochran, James D Baleja, Inna Lomakin, Xue Zhang, Annette Shepard-Barry, Arthur S Tischler","doi":"10.1530/ERC-25-0022","DOIUrl":"10.1530/ERC-25-0022","url":null,"abstract":"The RS0 cell line is a rat-derived pheochromocytoma line developed as a model to study pheochromocytoma/paraganglioma caused by hereditary mutations of the SDHB gene. Previous studies demonstrated that xenografts of the RS0 parent tumor replicate characteristics of their human counterparts, including loss of SDHB and upregulation of genes in hypoxia signaling pathways activated by EPAS1/HIF2A. Establishment of the cell line required a low O2 concentration, as cell proliferation was arrested in a traditional cell culture atmosphere of 20% O2. The present study profiled the effects of 20% versus 5% O2 and EPAS1/HIF2A inhibitors on the RS0 cell phenotype and tested how RS0 cells cultured under these influences compare to their parent xenografts and normal rat adrenal medulla. O2 concentration in cell cultures influences almost every aspect of the cells' biology, most obviously proliferation but also ultrastructure, transcriptome, metabolism and endocrine function. The cells most closely resemble their xenografts when maintained in a low O2 environment, but some differences between the cells in vivo and in vitro are not fully explained. Genes downregulated in high O2 are predominantly associated with the cell cycle, while those upregulated in low O2 include stemness and neuronal progenitor markers that may have contributed to the establishment of the cell line, as well as drug targets expressed in human pheochromocytoma/paraganglioma. Some effects of high O2 are mimicked by EPAS1/HIF2A inhibitors currently considered for treatment of metastatic Sdh-deficient PPGL, while others may be HIF-independent. The cytostatic effect of EPAS1/HIF2A inhibitors is reversible, suggesting possible limits to their usefulness as monotherapies.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047263","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

Refining long-term surveillance requirements in patients with differentiated thyroid cancer. 细化分化型甲状腺癌患者的长期监测要求。

Endocrine-related cancer Pub Date : 2025-06-03 Print Date: 2025-06-01 DOI: 10.1530/ERC-25-0046

Sam Arman, Marcus Lyall, Iain Nixon

{"title":"Refining long-term surveillance requirements in patients with differentiated thyroid cancer.","authors":"Sam Arman, Marcus Lyall, Iain Nixon","doi":"10.1530/ERC-25-0046","DOIUrl":"10.1530/ERC-25-0046","url":null,"abstract":"Differentiated thyroid cancer (DTC) has an excellent long-term prognosis following treatment. Despite this, post-treatment surveillance may last several years with no defined end-point. The aim of our study was to identify patients at the lowest risk of recurrence and suitable for early discharge. We conducted a retrospective analysis of a single centre database of all patients undergoing surgery for DTC between 2009 and 2022. We excluded patients with distant metastasis or those without a Tg level two years after complete thyroidectomy. Patients were grouped into hemithyroidectomy (H), total thyroidectomy (TT) and total thyroidectomy with radioactive ablation (TTR). TT and TTR groups were risk stratified using the Tg level at 2-year into undetectable/low (UL) (Tg < 0.2), medium (M) (0.2-1.0) and high (H) (>1.0). The 2015 American Thyroid Association (ATA) risk stratification system was used to further subdivide these groups. 481 patients were included in the study. The overall structural recurrence rate was 19/481 (3.9%) over a median follow-up period of 64 months (1-164). All recurrences occurred in the TTR group, with a median time to recurrence of 21 months. A higher Tg at 2-year (P < 0.00001) and a high ATA risk 2015 score (P = 0.007) were associated with higher rate of recurrence. Based on ATA guidelines, 100 patients were identified as low risk in the UL group, and there were no recurrences during the follow-up period. Our study suggests that individuals managed with hemithyroidectomy alone or with undetectable/low Tg levels within 2-year of treatment may be suitable for early discharge.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176211","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

Real-world effectiveness of darolutamide in metastatic castration-resistant prostate cancer. darolutamide在转移性去势抵抗性前列腺癌中的实际疗效。

Endocrine-related cancer Pub Date : 2025-05-29 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0188

Alyssa Liang, Shuchi Gulati, Quillan Huang, Heidi Dowst, Aedric Lim, Neda Zarrin-Khameh, Guilherme Godoy, Attiya B Noor, Patricia Castro, Michael E Scheurer, Mamta Parikh, Primo N Lara, Susan Hilsenbeck, Martha Mims, Nicholas Mitsiades

{"title":"Real-world effectiveness of darolutamide in metastatic castration-resistant prostate cancer.","authors":"Alyssa Liang, Shuchi Gulati, Quillan Huang, Heidi Dowst, Aedric Lim, Neda Zarrin-Khameh, Guilherme Godoy, Attiya B Noor, Patricia Castro, Michael E Scheurer, Mamta Parikh, Primo N Lara, Susan Hilsenbeck, Martha Mims, Nicholas Mitsiades","doi":"10.1530/ERC-24-0188","DOIUrl":"10.1530/ERC-24-0188","url":null,"abstract":"Darolutamide is a second-generation androgen receptor (AR) antagonist (2GARA) with established benefit in treating patients with non-metastatic castration-resistant prostate cancer (M0-CRPC) and metastatic castration-sensitive prostate cancer. Its real-world effectiveness in the treatment of patients with metastatic (M1) CRPC, including those who have progressed on CYP17 inhibitors (CYP17Is) or other 2GARAs (enzalutamide/apalutamide), is not well-described. We assessed the real-world effectiveness of darolutamide in a racially diverse cohort of 44 M1-CRPC and 11 M0-CRPC patients and collected data on baseline and emerging AR mutations in circulating tumor DNA (ctDNA) in these patients. The median progression-free survival (PFS) was 2.15 months for M1-CRPC and 21.16 months for M0-CRPC patients. In the M1-CRPC cohort, the median PFS was longer in those who had only received prior CYP17Is compared to 2GARA-resistant patients (2.43 vs 1.61 months; P = 0.03). Darolutamide suppressed serum PSA levels by >50% in 5/44 M1-CRPC patients (11.4%), all previously 2GARA-naïve. M1-CRPC patients resistant only to CYP17Is had improved mean best percent PSA changes from baseline compared to 2GARA-resistant patients (4.68 vs 42.34%; P = 0.047). PFS was not significantly different between African-American and non-African-American patients, or between patients with and without AR mutations at baseline. AR mutations emerging or increasing in allele fraction in ctDNA upon darolutamide treatment included H875Y, H100Q, D891H, T878A, L702H, L329W, N767Y and AR copy number gain. In summary, darolutamide may provide some benefit in CYP17I-refractory M1-CRPC patients, even in the presence of AR mutations. Resistance to other 2GARAs may significantly decrease benefit from darolutamide.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012051","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

Efficacy and safety of RET-kinase inhibitors in RET-altered thyroid cancers: a systematic review and single-arm meta-analysis. ret激酶抑制剂治疗ret改变的甲状腺癌的疗效和安全性：一项系统评价和单臂荟萃分析

Endocrine-related cancer Pub Date : 2025-05-29 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0219

Israt Jahan Riya, Ifrat Jahan Piya, Jonathan N Priantti, Cha Len Lee, Lina Barman, Almunthir Altobi

{"title":"Efficacy and safety of RET-kinase inhibitors in RET-altered thyroid cancers: a systematic review and single-arm meta-analysis.","authors":"Israt Jahan Riya, Ifrat Jahan Piya, Jonathan N Priantti, Cha Len Lee, Lina Barman, Almunthir Altobi","doi":"10.1530/ERC-24-0219","DOIUrl":"10.1530/ERC-24-0219","url":null,"abstract":"The RET proto-oncogene, which encodes a receptor tyrosine kinase, is an important factor in the pathogenesis of medullary and papillary thyroid cancers. Selpercatinib and pralsetinib, both specific RET-kinase inhibitors, are the only FDA-approved drugs for treating RET-altered thyroid cancer. We wanted to evaluate the safety and efficacy of selpercatinib and pralsetinib in RET-altered thyroid cancers. We searched the PubMed, Embase, Cochrane, and Clinicaltrials.gov databases for randomized controlled trials and observational studies published up to March 30, 2024, and included those that reported any of the desired endpoints. The primary endpoints were 1-year progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Quantitative analyses were performed using the R programming language. We included four studies with 560 patients, 510 with RET-mutant and 50 with RET-fusion thyroid cancer. The 1-year PFS was 84% (95% CI, 79-88, I 2 = 43%), ORR was 69% (95% CI, 65-73, I 2 = 0) and DCR was 93% (95% CI, 89-96, I 2 = 44%). Some important grade ≥3 adverse events were hypertension (16%; 95% CI, 11-22; I 2 = 43%), diarrhea (3%; 95% CI, 2-5; I 2 = 0), increased ALT (11%; 95% CI, 8-14; I 2 = 0) and increased AST (6%; 95% CI, 4-10; I 2 = 0). In conclusion, these findings suggest that selpercatinib and pralsetinib are efficacious and safe for use in patients with RET-altered thyroid cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046315","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

Differential activity of specific inhibitors of transcription regulating cyclin-dependent kinases in thyroid cancer cells. 甲状腺癌细胞中调节周期蛋白依赖性激酶的特异性转录抑制剂的差异活性。

Endocrine-related cancer Pub Date : 2025-05-29 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0124

Neel Rajan, Tilak Khanal, Amy Adik, Anisley Valenciaga, Akanksha Nigam, Sandya Liyanarachchi, Matthew D Ringel

{"title":"Differential activity of specific inhibitors of transcription regulating cyclin-dependent kinases in thyroid cancer cells.","authors":"Neel Rajan, Tilak Khanal, Amy Adik, Anisley Valenciaga, Akanksha Nigam, Sandya Liyanarachchi, Matthew D Ringel","doi":"10.1530/ERC-24-0124","DOIUrl":"10.1530/ERC-24-0124","url":null,"abstract":"'Superenhanced' transcription of oncogenes by aberrant looping of upstream enhancer elements to transcriptional regulatory regions is a mechanism of oncogene overexpression. Non-selective cyclin-dependent kinase inhibitors (CDKi) that target transcriptionally regulatory CDKs, including CDK7, 9, 12 and 13, reduce mRNA levels of super-enhanced oncogenes and have activity against thyroid cancer cells. We hypothesized that more specific inhibitors of CDKs would have differential activities in thyroid cancer cells and may be suitable for further studies. We selected thyroid cancer cell lines with a variety of genetic drivers for initial screening studies with CDK7/12/13 (THZ1) and CDK9 (AZD4573) inhibitors. IC50 values ranged from 5 to 100 nM for THZ1 for all cell lines and six of eight cell lines for AZD4573, with inhibition of RNAPII phosphorylation and evidence of reduced cell migration. Four thyroid cancer cell lines with common driver mutations, including 8505C (BRAFV600E), BCPAP (BRAFV600E), TPC1 (RET fusion) and FTC133 (PTEN null), were selected for detailed studies with more specific inhibitors. In these cells, the CDK 12/13 inhibitor (SR-4835) and AZD4573 were more effective than the specific CDK7 inhibitor YKL-5-124 at reducing cell survival, migration and proliferation, and at inducing apoptosis. Treatment with SR-4835 was the most potent, induced DNA damage and resulted in cyclin K loss. Combined reduction in CDK12/13 levels with siRNA reduced RNAPII phosphorylation. These data suggest that specific inhibitors of CDK12/13 may be particularly active in thyroid cancer cell lines; further studies evaluating their efficacy are warranted in thyroid cancer.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059780","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

ERRATUM: Roles of the HOXA10 gene during castrate-resistant prostate cancer progression. 错误：HOXA10基因在去势抵抗性前列腺癌进展中的作用。

Endocrine-related cancer Pub Date : 2025-05-15 Print Date: 2025-06-01 DOI: 10.1530/ERC-18-0465e

Zhi Long, Yinan Li, Yu Gan, Dongyu Zhao, Guangyu Wang, Ning Xie, Jessica M Lovnicki, Ladan Fazli, Qi Cao, Kaifu Chen, Xuesen Dong

引用次数: 0

In vivo and in vitro analysis of functional effects of the SDHD H50R variant. sddd H50R变异的体内外功能效应分析。

Endocrine-related cancer Pub Date : 2025-05-14 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0337

Shivam Priya, Karthik Chakravarthy, Edward Ziegler, Xavier Vesco, Krista La Perle, Xiaoli Zhang, Lawrence S Kirschner

{"title":"In vivo and in vitro analysis of functional effects of the SDHD H50R variant.","authors":"Shivam Priya, Karthik Chakravarthy, Edward Ziegler, Xavier Vesco, Krista La Perle, Xiaoli Zhang, Lawrence S Kirschner","doi":"10.1530/ERC-24-0337","DOIUrl":"10.1530/ERC-24-0337","url":null,"abstract":"Germline mutations in the four genes (SDHA, SDHB, SDHC and SDHD) encoding the succinate dehydrogenase (SDH) holoenzyme are known to predispose towards the development of tumor including pheochromocytomas/paragangliomas (PPGLs), gastrointestinal stromal tumors (GISTs), clear cell renal cancers (RCC) and possibly others. Mutations in these genes have also been described in patients with Cowden syndrome, which includes tumors of the breast, brain and thyroid gland. Although nonsense mutations are clearly pathogenic, the functional consequences of many missense mutations are unclear. It has previously been reported that the missense mutations SDHDG12S and SDHDH50R predispose to thyroid and breast cancers, although this characterization has been disputed. To address this question, we developed mouse models to test tumorigenicity of these variants. The reference mouse genome codes for a serine at residue 12 in Sdhd, so this variant was not pursued further. To assess the role of SDHDH50R (H50R), we generated a knock-in mouse allele for this variant and studied its effects in vivo as well as in vitro in mouse embryonic fibroblasts. Unlike null alleles for Sdhd, the H50R allele did not produce embryonic lethality when homozygous. There was no statistically significant difference in survival or tumor formation in homozygous or heterozygous animals compared to littermate controls. In vitro studies similarly failed to detect significant differences in proliferation, colony formation or metabolic function. Based on our analysis of this allele's function both in vivo and in vitro, we conclude that the SDHDH50R allele is most likely a non-pathogenic polymorphism.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028230","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

Clinicopathological characteristics associated with the prognosis of recurrent gonadotroph tumors. 复发性性腺功能瘤的临床病理特征与预后的关系。

Endocrine-related cancer Pub Date : 2025-05-13 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0186

Chrysi Kaparounaki, Alexandre Vasiljevic, Emmanuel Jouanneau, Camille Sergeant, Gérald Raverot, Mirela-Diana Ilie

{"title":"Clinicopathological characteristics associated with the prognosis of recurrent gonadotroph tumors.","authors":"Chrysi Kaparounaki, Alexandre Vasiljevic, Emmanuel Jouanneau, Camille Sergeant, Gérald Raverot, Mirela-Diana Ilie","doi":"10.1530/ERC-24-0186","DOIUrl":"10.1530/ERC-24-0186","url":null,"abstract":"Although gonadotroph tumor regrowth is frequent after pituitary surgery, the systematic use of adjuvant radiotherapy is limited by its long-term complications. In this context, it is important to predict which tumors are most likely to regrow after surgery, and especially, which tumors are most likely to regrow rapidly. Clinicopathological characteristics associated with the prognosis of radiotherapy-naïve, recurrent pituitary tumors are currently unknown. In this longitudinal, observational, retrospective, monocentric cohort study, we analyzed the clinicopathological characteristics associated with the prognosis of recurrent, radiotherapy-naïve gonadotroph tumors, specifically with the progression-free survival after a second pituitary surgery. We found that the Ki67 index of radiotherapy-naïve, recurrent gonadotroph tumors was the only parameter statistically associated with the progression-free survival after a second pituitary surgery, P = 0.02. Specifically, radiotherapy-naïve gonadotroph tumors with a positive Ki67 index had shorter progression-free survival after the second surgery (median 31 months) compared to radiotherapy-naïve gonadotroph tumors with a negative Ki67 index (median 75 months). Thus, our study pinpoints that the Ki67 index could be used to guide the management strategy for recurrent gonadotroph tumors that are still radiotherapy-naïve by the time of the second pituitary surgery.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055956","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

Surrogate molecular classification of LAR breast cancer in routine workflow. 常规工作流程中LAR乳腺癌的替代分子分类。

Endocrine-related cancer Pub Date : 2025-05-05 Print Date: 2025-06-01 DOI: 10.1530/ERC-24-0316

Nelson Rangel, Laura Serrao, Giulia Capella, Giulia Orlando, Federica Ragno, Milena Rondón-Lagos, Jasna Metovic, Paola Cassoni, Isabella Castellano

{"title":"Surrogate molecular classification of LAR breast cancer in routine workflow.","authors":"Nelson Rangel, Laura Serrao, Giulia Capella, Giulia Orlando, Federica Ragno, Milena Rondón-Lagos, Jasna Metovic, Paola Cassoni, Isabella Castellano","doi":"10.1530/ERC-24-0316","DOIUrl":"10.1530/ERC-24-0316","url":null,"abstract":"Triple negative breast cancer (TNBC) is a heterogeneous disease, considered the most aggressive among all diagnosed breast cancers. The luminal androgen receptor (LAR) category has been recognized as a distinct entity (subtype), observed in around 15% of the TNBCs, but currently there is no complete overlap to clearly distinguish them from the other TNBC counterparts. With the aim to better establish morphological, immunohistochemical and molecular features of LAR tumors, gene and signatures expression was evaluated in 42 well-characterized TNBCs. Furthermore, protein expression of a panel of several markers (AR, FOXA1, CK5/6, p63, GCDFP-15 and FGFR4) was also studied. Compared with non-LAR cases, LAR tumors often display low tumor grade, reduced levels of Ki-67, total absence of CK5/6 and p63 basal markers expression, but show high positivity for AR, FOXA1 and FGFR4. Regarding molecular assessment, LAR tumors were characterized by higher scores of gene signatures associated with AR, FOXA1 and ERBB2, while showed lower scores of signatures related to BC proliferation, CDK6, BRCAness and p53. Our results suggest that among TNBC, LAR cases are associated with features indicative of a less aggressive tumor behavior. Accurate distinction of this TNBC subtype is important since they are resistant to chemotherapy and may potentially benefit from tailored-therapeutical approaches. Specifically, therapies targeting AR together to additional proteins, such as FGFR4, FOXA1 or CDK6, may represent future directions in the treatment approach of LAR tumors.","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":"32 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001946","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