Endocrine Abstracts

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...

Standard treatment of adrenocortical carcinoma (ACC) comprises adrenolytic therapy with mitotane. Prolongation of bleeding time has previously been observed based on a series of 7 patients (Haak et al. 1991). As patients with ACC frequently undergo surgery for local recurrence or metastases, we have studied the effect of mitotane on coagulation in 44 patients with ACC before and/or during treatment with mitotane (total sample size n=62).Pla...

Adrenal masses are highly prevalent tumours comprising of a variety of entities. Therefore, therapeutic consequences also vary considerably. The CYP11B-specific PET-tracer [11C]metomidate has been shown to be suitable to characterize adrenal lesions. However, its availability is restricted to PET-centers with an on-site cyclotron. Also imaging is hindered by the short tracer half-life (20 min). Therefore, we have developed [123I]iodometomidate as a tracer...

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...

Protein Kinase A (PKA) consists of two catalytic and two regulatory subunits with several isoforms (Cα, β, γ and RIα, IIα, Iβ, IIβ, respectively). Type II regulatory subunits are phosphorylated by PKA in their inhibitory sites, while type I are not. Somatic activating mutations in the gene encoding the catalytic subunit α (Cα) of PKA (PRKACA) have been found in 30–40% of cortisol-producing adrenocortical adenomas (CPA). We rece...

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...

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...