Endocrine Abstracts

Introduction: Adrenocortical carcinoma (ACC) is an aggressive tumour with unsatisfactory treatment options in advanced disease. Activation of epithelial to mesenchymal transition (EMT) has been described as causative of metastatic spread in human cancers. New drugs were developed targeting EMT with a focus on FGF/FGFR signalling. We here asked whether EMT is relevant in ACC.Methods: We analysed 6 normal adrenal glands (NAG), 40 adrenocortical adenomas (A...

Objectives: No immunohistochemical marker has yet been established to reliably differentiate adrenocortical tumors from other adrenal masses (e.g. metastases). Thus, a panel of several markers like melan A and inhibin is currently used for this purpose, but suffers from limited diagnostic accuracy. We hypothesized that expression of steroidogenic factor 1 (SF-1), a nuclear transcription factor involved in adrenal development and steroidogenesis, might hold significant diagnost...

Adrenocortical carcinoma (ACC) is a malignant tumor with poor prognosis and no established therapy in advanced stage. Cisplatin is the most frequently used cytotoxic drug, but even combined with doxorubicin and etoposid, the response rate is <50%. Recently, it has been demonstrated that the excision repair cross complementing group 1 (ERCC1) plays a relevant role in the DNA repairing process, particularly in the correction of platinum-induced DNA adducts. Accordingly, ERCC...

Objectives: Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis and limited therapeutic options. Survivin is an anti-apoptotic molecule expressed by neoplastic and tumor-specific endothelial cells of various carcinomas, but rarely or only weakly in normal differentiated tissue. In melanoma and pancreatic cancer, preliminary results of a survivin vaccination trial (www.clinicaltrials.gov) indicated that an immunological response in patients is often paralleled by...

We previously identified mutations in PRKACA, coding for the catalytic a (Ca) subunit of protein kinase A (PKA), as the main genetic alteration in cortisol-producing adrenal adenomas (CPAs) responsible for Cushing’s syndrome. Here, we further investigated the mechanism of action of all PRKACA mutations identified so far by our team (L206R, L199_C200_insW, S213R_L212_K214insIILR, C200_GlyinsV, W197R, del244-248+E249Q and E32V). Five out of seven mutants s...

Adrenocortical carcinomas (ACC) are associated with heterogeneous prognosis and limited treatment options for advanced stages. Until now no efficient targeted therapies have been identified. This study aims to identify possible new molecular drug targets for a future personalized therapeutic approach. We isolated good quality RNA from 40 formalin-fixed paraffin-embedded tumor samples (33 from primary surgery, 5 from local recurrences and 2 from distant metastasis) of ACC patie...

Introduction: Transcriptional regulation of gene expression by miRNAs is critical for the fine-tuning of adrenal stress response. However, its role in hypercortisolism has not been explored well. The study addresses this gap using adrenal samples of 3 patient groups from the German Cushing’s registry: Cortisol-Producing-Adenoma (CPA), Primary Bilateral Adrenal Hyperplasia (PBMAH) and controls (adrenal samples of patients with pheochromocytoma).Metho...

Background: Adrenocortical carcinoma (ACC) is one of the most aggressive endocrine malignancies. The Fibroblast Growth Factor/Fibroblast Growth Factor Receptor (FGF/FGFR) pathway plays a role in both embryogenesis and tumorigenesis of adrenal gland. Our group demonstrated that FGFR1-4 were upregulated in ACCs and that their high expression was significantly associated with worse prognosis, suggesting that they are potentially interesting therapeutic targets.<p class="abste...

BackgroundAdrenocortical carcinoma (ACC) is a rare but devastating tumour of the adrenal gland and the molecular mechanisms of pathogenesis remain incompletely understood. To gain novel insights into the cellular landscape of ACC, we compared single nuclei RNA sequencing (snRNA-seq) datasets from ACC and normal adrenal glands (NAGs).Methods: We isolated single nuclei from 12 ACC snap-frozen samples, including 6 primary tumours, 3 local r...

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine disease in which 60% of patients show endogenous glucocorticoid (GC) secretion that potentially contributes to a lack of immune cell infiltration and limited efficacy of immunotherapeutic approaches. In another study, we already demonstrated potent antitumor efficacy or ROR1 CAR-T cells in preclinical models of ACC. Nevertheless, solid tumors often show cell intrinsic resistance mechanisms to CAR-T c...