Endocrine Abstracts

The role of luteinizing hormone (LH) and its receptor (LHCGR) signaling in the adrenal gland remains unknown. Gonadectomy-induced chronically elevated LH levels trigger neoplastic transformation in genetically susceptible mouse strains (DBA/2J) or transgenic mice expressing the Simian Virus 40 T antigen (SV40Tag) oncogene under inhibin-α promoter (inhα/Tag). In order to study the functional role of LHR and GATA4 in the onset and progression of adrenocortical tumors i...

Adrenocortical carcinoma (ACC) is a rare tumor with heterogeneous outcome and no available targeted therapy. The aim of the study is to identify prognostic molecular markers and novel potential drug targets.A total of 43 FFPE tumor samples were retrospectively investigated for somatic mutations and copy number variations (CNV) by next-generation sequencing (160 cancer-related genes, Qiagen). Gene expression was evaluated by quantitative RT-PCR in a subgr...

Introduction: The Carney Complex is a multiple endocrine and non endocrine neoplasia mostly due to PRKAR1A mutations. Spectrum of manifestations and genotype-phenotype correlations have been previously described by retrospective studies. A prospective study evaluating the occurrence of the different manifestations was needed to precise the optimum follow-up.Methods: Multi-center national prospective study (Clinical Trials NCT00668291) including 70 patien...

Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. By applying a ‘multiple omics’ approach, we recently identified two distinct subgroups of ACC patients, a good prognosis “immune” and bad prognosis “steroid” phenotype.We hypothesized that the steroid phenotype is associated with glucocorticoid-induced suppression that can be ‘rescued’ by reactivating the immune system using immune...

Background: Adrenal masses are discovered in 5% of abdominal imaging scans. Work-up aims at exclusion of malignancy and hormone excess. However, estimates of these risks derive from retrospective studies only, mostly small and with significant selection bias.Methods: Prospective multi-centre study (2011–2016) in 14 centres (11 countries) of the European Network for the Study of Adrenal Tumours (ENSAT) with prospective consecutive enrolment of patien...

Background: Adjuvant mitotane therapy is frequently used in Europe following surgery for adrenocortical carcinoma (ACC). Management of adjuvant mitotane is mainly empirical and a major open question is the optimal duration of therapy, because no study has ever addressed this issue.Objective: We aimed to assess the outcome of ACC patients who were treated with adjuvant mitotane for at least one year following surgery and then discontinued therapy for othe...

Background: About 8–20% of patients with von Hippel-Lindau disease (vHLd) develop pancreatic neuroendocrine tumors (PNETs). However, prognostic markers for these tumors are lacking. The VHL gene mutation type is associated with the clinical phenotype of vHLd. Hence, we aimed to determine whether VHL mutation characteristics may be associated with PNETs phenotype in patients with vHLd.Methods: A prospective study of patients with vHLd and PNETs with ...

Colorectal cancer (CRC) is the 2nd most commonly diagnosed cancer in Europe. Previously, we have shown steroid sulphatase (STS), the enzyme that converts conjugated oestrogens to their active forms, is significantly upregulated in human CRC tissue. Furthermore, increased STS activity substantiates greater CRC tumour burden in mouse models. Here we demonstrate that this oestrogen-induced increase of CRC proliferation is mediated by G-protein coupled oestrogen receptor (GPER) vi...

The unresponsiveness of anaplastic thyroid carcinomas (ATCs) to multimodal therapy represents the major challenge in thyroid cancer treatment. Our group previously showed that genes involved in cell cycle are differentially expressed in ATCs compared to normal thyroid, and that the most common mutations found in these tumours are related with proliferation and cell cycle genes, namely TP53, RAS, CDKN2A and CDKN2B. Therefore, these genes are ...

Metabolic Syndrome (MetS) has been frequently associated with an overall inflammation status, called “metaflammation”, including atherosclerosis and non-alcholic steatohepatitis (NASH), In this study we aimed to evaluate the relationship between intra-prostatic inflammation and NASH in a cohort of patients affected by BPH. Between January 2012 and January 2016, 132 consecutive patients with BPH-related lower urinary tract symptoms (LUTS) who underwent transurethral r...

A growing number of studies suggest that extracellular fragments derived from plasma membrane receptors can play relevant functional roles in the development and progression of certain tumoral pathologies which might, therefore, serve as novel tools in the diagnostic and prognostic of such pathologies. In this scenario, the truncated somatostatin receptor sst5TMD4, which is overexpressed in various endocrine-related cancers (i.e. breast, prostate, neuroendocrine, liver and pit...

The effect of androgen on angiogenesis has been documented. However, its molecular mechanisms underlying has not been well illustrated. Here, we show that treatment with an androgen receptor (AR) agonist, metribolone (R1881) at a range of concentrations (0.05–5 nM) or dihydrotestosterone (DHT) at a range of concentrations (0.4–40 nM) caused concentration-dependent inhibition of proliferation in human umbilical venous endothelial cells (HUVEC). The R1881-induced proli...

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