Search for other papers by Sijin Li in
Google Scholar
PubMed
Search for other papers by Zhen Chen in
Google Scholar
PubMed
Search for other papers by Mengchu Liu in
Google Scholar
PubMed
Search for other papers by Liang Li in
Google Scholar
PubMed
Search for other papers by Wensong Cai in
Google Scholar
PubMed
Search for other papers by Zhe-Xiong Lian in
Google Scholar
PubMed
Search for other papers by Haixia Guan in
Google Scholar
PubMed
Search for other papers by Bo Xu in
Google Scholar
PubMed
The activation of Treg cell subsets is critical for the prognosis of tumor patients; however, their heterogeneity and disease association in papillary thyroid carcinoma (PTC) need further investigation. We performed high-dimensional flow cytometry for immunophenotyping on thyroid tissues and matched peripheral blood samples from patients with multinodular goiters or PTC. We analyzed CD4+ T cell and Treg cell phenotypes and compared the recurrence-free survival of PTC patients with different Treg cell subset characteristics using TCGA. Furthermore, PTC recurrent and non-recurrent group were compared by multiplex immunohistochemistry. High-dimensional flow cytometry and bioinformatics analysis revealed an enrichment of Tregs in tumors compared with multinodular goiters and peripheral blood specimens. Moreover, effector Tregs (e-Tregs) as well as FOXP3+ non-Tregs were enriched in tumor samples, and the expression of CD39, PD-1, and CD103 increased on tumor Tregs. TCGA data analysis showed that individuals with CD39hi PD-1loCD103loe-Treghi and CD39loPD-1loCD103hie-Treghi expression patterns had a high recurrence rate. According to the multiplex immunohistochemistry and analysis, compared with non-recurrent group, the proportion of high recurrence rate effector Treg clusters (CD39+PD-1−CD103− plus CD39−PD-1−CD103+) was increased in recurrent patients. Overall, our results highlight the potential of e-Treg subsets as future immunotherapy targets for PTC recurrence.
Department of Clinical Research, University of Basel, Basel, Switzerland
Search for other papers by Julia Beck in
Google Scholar
PubMed
Search for other papers by Alexander Siebenhüner in
Google Scholar
PubMed
Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland
Search for other papers by Damian Wild in
Google Scholar
PubMed
Department of Clinical Research, University of Basel, Basel, Switzerland
Search for other papers by Emanuel Christ in
Google Scholar
PubMed
Department of Clinical Research, University of Basel, Basel, Switzerland
Search for other papers by Julie Refardt in
Google Scholar
PubMed
Sex differences affect the management of several diseases in both male and female patients. However, the influence of sex on neuroendocrine neoplasms (NENs) has been scarcely investigated. Thus, this study aimed to compare tumor characteristics, treatment decisions, and overall survival in patients with NENs, stratified by sex. The retrospective analysis of the SwissNET cohort covered NENs of gastroenteropancreatic, pulmonary, or unknown origin from July 2014 to September 2022. The analysis included 1985 patients (46% female and 54% male). No significant difference in tumor grading was found between male and female patients. However, male patients presented with higher staging at time of diagnosis and with more lymph node and bone metastases. Surgery was performed more often in female compared to male patients (73.4% vs 68.7%, P = 0.023). Male patients received peptide receptor nuclide therapy (PRRT) earlier than female patients (7.8 months vs 13.1 months from time of diagnosis, P = 0.003). The median overall survival was significantly shorter for male compared to female patients (male: 18 years, female: not reached, P < 0.001, hazard ratio (HR) 1.55 (1.19–2.01), P = 0.001). Multivariable analyses revealed advanced age (HR 1.02 (1.01–1.04)), cancer of unknown origin (HR 2.01 (1.09–3.70)), higher grading (G3: HR 6.74 (4.22–10.76)), having metastases at the time of diagnosis (HR 2.11 (1.47–3.02)), and surgical treatment (HR 0.67 (0.48–0.93)) as independent predictors for overall survival. In conclusion, male sex was associated with worse outcome in NEN patients, likely due to more advanced tumor stage at the time of diagnosis. Further investigations are required to understand the underlying mechanisms of these sex differences.
Department of Urology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China
Search for other papers by Yihao Chen in
Google Scholar
PubMed
Search for other papers by Jiahong Chen in
Google Scholar
PubMed
Search for other papers by Yongcheng Shi in
Google Scholar
PubMed
Search for other papers by Xiaohui Ling in
Google Scholar
PubMed
Search for other papers by Shumin Fang in
Google Scholar
PubMed
Search for other papers by Chuanfan Zhong in
Google Scholar
PubMed
Search for other papers by Fengping Liu in
Google Scholar
PubMed
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China
Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, Guangdong
Search for other papers by Weide Zhong in
Google Scholar
PubMed
Search for other papers by Xuecheng Bi in
Google Scholar
PubMed
Search for other papers by Zhong Dong in
Google Scholar
PubMed
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China
Search for other papers by Jianming Lu in
Google Scholar
PubMed
Adrenocortical carcinoma (ACC) is a malignancy with a poor prognosis and high mortality rate. A high tumor mutational burden (TMB) has been found to be associated with poor prognosis in ACC. Thus, exploring ACC biomarkers based on TMB holds significant importance for patient risk stratification. In our research, we utilized weighted gene coexpression network analysis and an assay for transposase-accessible chromatin with high-throughput sequencing to identify genes associated with TMB. Through the comprehensive analysis of various public datasets, Lamin B1 (LMNB1) was identified as a biomarker associated with a high TMB and low chromatin accessibility. Immunohistochemical staining demonstrated high expression of LMNB1 in ACC compared to noncancerous tissues. Functional enrichment analyses revealed that the function of LMNB1 is associated with cell proliferation and division. Furthermore, cell assays suggested that LMNB1 promotes tumor proliferation and invasion. In addition, mutation analysis suggested that the high expression of LMNB1 is associated with TP53 mutations. Additionally, LMNB1 was highly expressed in the vast majority of solid tumors across cancers. In our immune analysis, we discovered that the high expression of LMNB1 might suppress the infiltration of CD8+ T cells in the ACC microenvironment. In summary, LMNB1 is a predictive factor for the poor prognosis of adult and pediatric ACC. Its high expression in ACC is positively associated with high TMB and lower chromatin accessibility, and it promotes ACC cell proliferation and invasion. Therefore, LMNB1 holds promise as a novel biomarker and potential therapeutic target for ACC.
Search for other papers by Andreas Machens in
Google Scholar
PubMed
Search for other papers by Kerstin Lorenz in
Google Scholar
PubMed
Search for other papers by Frank Weber in
Google Scholar
PubMed
Department of General, Visceral and Transplantation Surgery, Division of Endocrine Surgery, University of Duisburg-Essen, Essen, Germany
Search for other papers by Henning Dralle in
Google Scholar
PubMed
Thyroid cancer is the only nonreproductive cancer with striking female predominance, although men with thyroid cancer develop more aggressive disease. This study aimed to quantify sex-specific differences in medullary thyroid cancer (MTC) spread after controlling for primary thyroid tumor size. Included in this retrospective analysis were all patients with unilateral solitary MTC who underwent initial neck surgery at a tertiary referral center. A total of 565 patients, 255 men and 310 women, were identified, of whom 467 had sporadic and 98 hereditary MTC. When stratified by sex, and after correction for multiple testing, men had higher preoperative basal calcitonin levels (medians of 655 vs 181 pg/mL; P < 0.001), more frequent extrathyroid extension (25 vs 9%; P < 0.001) and node metastasis (53 vs 27%; P < 0.001) with more involved nodes (medians of 2 vs 0 nodes; P < 0.001) than women but achieved less often biochemical cure (53 vs 74%; P < 0.001). Although absent in patients with very small (≤5 mm) thyroid tumors, sex disparities were immediately apparent in patients with 5.1–40 mm (node metastasis and biochemical cure) and 10.1–40 mm (extrathyroid extension) large thyroid tumors but were lost in patients with thyroid tumors >40 mm as women caught up. Sex disparities were strongest for node metastasis with a 27–41% (overall 24.0%) point difference, followed by biochemical cure with a −15–35% (overall −20.3%) point difference and extrathyroid extension with a 17–24% (14.2% overall) point difference. These findings indicate that the male predominance in MTC aggressiveness is largely biologically driven, warranting further research.
Search for other papers by Uriel Clemente-Gutierrez in
Google Scholar
PubMed
Search for other papers by Carolina R C Pieterman in
Google Scholar
PubMed
Search for other papers by Michael S Lui in
Google Scholar
PubMed
Search for other papers by Thomas Szabo Yamashita in
Google Scholar
PubMed
Search for other papers by Andrés Tame-Elorduy in
Google Scholar
PubMed
Search for other papers by Bernice L Huang in
Google Scholar
PubMed
Search for other papers by Aditya S Shirali in
Google Scholar
PubMed
Search for other papers by Derek J Erstad in
Google Scholar
PubMed
Search for other papers by Jeffrey E Lee in
Google Scholar
PubMed
Search for other papers by Sarah B Fisher in
Google Scholar
PubMed
Search for other papers by Paul H Graham in
Google Scholar
PubMed
Search for other papers by Elizabeth G Grubbs in
Google Scholar
PubMed
Search for other papers by Steven G Waguespack in
Google Scholar
PubMed
Search for other papers by Chaan S Ng in
Google Scholar
PubMed
Search for other papers by Nancy Perrier in
Google Scholar
PubMed
Adrenal lesions (ALs) are often detected in patients with multiple endocrine neoplasia type 1 (MEN1). However, they are not well described in MEN1, making their clinical management unclear. This study examined the prevalence and outcomes of ALs found in MEN1. We performed a retrospective chart review of patients diagnosed with MEN1 from 1990 to 2021. ALs were diagnosed using abdominal or thoracic imaging and classified as being unilateral or bilateral, having single or multiple nodules, and as having diffuse enlargement or not. Measurable nodular lesions were analyzed for their size and growth over time. Patients’ clinical and radiographic characteristics were collected. We identified 382 patients with MEN1, 89 (23.3%) of whom had ALs. The mean age at detection was 47 ± 11.9 years. We documented 101 measurable nodular lesions (mean size, 17.5 mm; range, 3–123 mm). Twenty-seven nodules (26.7%) were smaller than 1 cm. Watchful waiting was indicated in 79 (78.2%) patients, of whom 28 (35.4%) had growing lesions. Functional lesions were diagnosed in 6 (15.8%) of 38 that had functional work-up (diagnoses: pheochromocytoma (n = 2), adrenocorticotropic hormone-dependent hypercortisolism (n = 2), hyperandrogenism (n = 1), hyperaldosteronism (n = 1)); surgery was indicated for 5 (83.3%; n = 12 nodules), 2 of whom had bilateral, diffuse adrenal enlargement. Two patients were diagnosed with adrenocortical carcinoma and two with neoplasms of uncertain malignant potential. Radiographic or clinical progression of ALs is uncommon. Malignancy should be suspected on the basis of a lesion’s growth rate and size. A baseline hormonal work-up is recommended, and no further biochemical work-up is suggested when the initial assessment shows nonfunctioning lesions.
Search for other papers by Roger Harty in
Google Scholar
PubMed
Search for other papers by Joshua D Safer in
Google Scholar
PubMed
Graphical abstract
Abstract
With the increasing number of transgender and gender diverse (TGD) individuals who are seeking gender-affirming care, there is a clear need for the development and collection of evidence-based data to establish guidelines for patient care. TGD individuals are estimated to represent 0.3 to 4.5% of the world population. Gender-affirming care that includes hormone therapy helps to align the body of a transgender person with their gender identity. Hormone therapy requires monitoring for both safety and efficacy. The extent to which gender-affirming hormone therapy alters cancer risk remains unknown. Because of a lack of comprehensive data collection pertaining to this patient population, endocrine cancer data including incidence and outcomes is limited. Dedicated research is needed to help address the gap in knowledge pertaining to the risk of cancer in the TGD population.
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal
Search for other papers by Valdemar Máximo in
Google Scholar
PubMed
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitário de Coimbra, Medical Faculty, University of Coimbra, Coimbra, Portugal
Search for other papers by Miguel Melo in
Google Scholar
PubMed
Search for other papers by Yingjie Zhu in
Google Scholar
PubMed
Search for other papers by Andrea Gazzo in
Google Scholar
PubMed
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal
Department of Pathology, Hospital São João, Porto 4200-319, Portugal
Search for other papers by Manuel Sobrinho Simões in
Google Scholar
PubMed
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Search for other papers by Arnaud Da Cruz Paula in
Google Scholar
PubMed
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal
Search for other papers by Paula Soares in
Google Scholar
PubMed
The genetic repertoire of primary thyroid cancers (TCs) is well documented, but there is a considerable lack of molecular profiling in metastatic TCs. Here, we retrieved and analyzed the molecular and clinical features of 475 primary and metastatic TCs subjected to targeted DNA sequencing, from the cBioPortal database. The cohort included primary and metastatic samples from 276 papillary thyroid carcinomas (PTCs), 5 follicular thyroid carcinomas, 22 Hürthle cell carcinomas (HCCs), 127 poorly differentiated thyroid carcinomas (PDTCs), 30 anaplastic thyroid carcinomas (ATCs) and 15 medullary thyroid carcinomas. The ATCs had the highest tumor mutational burden and the HCCs the highest fraction of the genome altered. Compared to primary PTCs, the metastases had a significantly higher frequency of genetic alterations affecting TERT (51% vs 77%, P < 0.001), CDKN2A (2% vs 10%, P < 0.01), RET (2% vs 7%, P < 0.05), CDKN2B (1% vs 6%, P < 0.05) and BCOR (0% vs 4%, P < 0.05). The distant metastases had a significantly lower frequency of BRAF (64% vs 85%, P < 0.01) and a significantly higher frequency of NRAS (13% vs 3%, P < 0.05) hotspot mutations than the lymph node metastases. Metastases from HCCs and PDTCs were found to be enriched for NF1 (29%) and TP53 (18%) biallelic alterations, respectively. The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, P < 0.01) and PDTCs (43% vs 22%, P < 0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.
Search for other papers by Isabella Albuquerque Pinto Rebello in
Google Scholar
PubMed
Search for other papers by Vinícius Loures de Oliveira in
Google Scholar
PubMed
Search for other papers by Luís Felipe Holzwarth Abbud in
Google Scholar
PubMed
Search for other papers by Tales Aprígio Camargos Ferreira in
Google Scholar
PubMed
Search for other papers by Ana Paula Aguiar Vidal in
Google Scholar
PubMed
Search for other papers by Patrícia de Fátima dos Santos Teixeira in
Google Scholar
PubMed
Few studies have focused on reclassifying follicular adenomas (FAs) as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), but none have been conducted in America or Europe. The aims of this study were to analyze the prevalence of NIFTP reclassified from follicular variant of papillary thyroid carcinomas (FVPTCs) and FAs before NIFTP was defined in the literature, the rate of NIFTP among PTC (papillary thyroid carcinomas) established in real time between 2017 and 2022, and demographic, ultrasonographic, and cytologic characteristics of NIFTPs compared with FVPTCs and FAs. This was a retrospective cohort study of tumors diagnosed as PTCs (n = 247) and FAs (n = 144) at a Brazilian hospital. Overall, 13.4% of PTCs and 7% of FAs were reclassified as NIFTPs. The rate of real-time diagnosed NIFTPs among PTC was 12.3%. The median tumor size was larger among NIFTPs (3.0 cm) than FVPTCs (1.1 cm; P < 0.01). A high-risk ultrasonographic pattern was rare in NIFTPs (5.6%). The cytologic classifications differed between FVPTCs and NIFTPs (P < 0.01), and the most frequent category among NIFTPs was ‘follicular neoplasm’ (52.6%). The category ‘suspicious for malignancy’ was frequent in FVPTCs and rare (5.3%) in NIFTPs. In conclusion, FVPTCs and FAs may be reclassified as NIFTPs. The prevalence of NIFTPs reclassified from FAs was lower in our cohort than in Asian studies. The rate of NIFTPs reclassified from PTC was similar to that of NIFTPs diagnosed in real time and was aligned with rates reported in studies from America and Europe. Preoperative features could not differentiate NIFTPs from FVPTCs or FAs.
Search for other papers by Andres Elía in
Google Scholar
PubMed
Search for other papers by Leo Saldain in
Google Scholar
PubMed
Search for other papers by Silvia Lovisi in
Google Scholar
PubMed
Search for other papers by Paula Martínez Vazquez in
Google Scholar
PubMed
Search for other papers by Javier Burruchaga in
Google Scholar
PubMed
Search for other papers by Caroline A Lamb in
Google Scholar
PubMed
Search for other papers by Isabel Alicia Lüthy in
Google Scholar
PubMed
Search for other papers by Federico Diez in
Google Scholar
PubMed
Search for other papers by Natalie Z M Homer in
Google Scholar
PubMed
Search for other papers by Ruth Andrew in
Google Scholar
PubMed
Search for other papers by Paola Rojas in
Google Scholar
PubMed
Search for other papers by Claudia Lanari in
Google Scholar
PubMed
Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they are still not used as therapeutic targets. We have proposed that the ratio between PR isoforms A and B (PRA and PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed the benefit of 200 mg mifepristone, administered to patients with tumors with a high PRA/PRB ratio, but dose-ranging has not been conducted. The aim of this study was to establish the plasma mifepristone levels of patients from the MIPRA trial, along with the resultant steroid profiles, and compare these with those observed in mifepristone-treated mice using therapeutic schemes able to induce the regression of experimental mammary carcinomas with high PRA/PRB ratios: 6 mg pellets implanted subcutaneously, or daily doses of 12 mg/kg body weight. The plasma levels of mifepristone and other 19 plasma steroids were measured by liquid chromatography–tandem mass spectometry. In mifepristone-treated mice, plasma levels were lower than those registered in mifepristone-treated patients (i.e. day 7 after treatment initiation, pellet-treated mice: 8.4 ± 3.9 ng/mL; mifepristone-treated patients: 300.3 ± 31.7 ng/mL (mean ± s.d.; P < 0.001)). The increase in corticoid related steroids observed in patients was not observed in mifepristone-treated mice. The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.
