Adrenocortical Carcinoma Research Articles

Identifying genomic signatures of recurrence in adrenocortical carcinoma after R0 resection

BackgroundAdrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited treatment options. Although there have been recent advancements revealing genomic drivers of these tumors, it remains unclear which genomic signatures are associated with recurrence, particularly following R0 resection. MethodsAdrenocortical carcinoma patients treated with adrenalectomy in the Cancer Genome Atlas with recurrence data were identified using cBioPortal. Clinicopathologic variables, genomics, treatment patterns, and outcomes were retrospectively analyzed. ResultsAmong 92 adrenocortical carcinoma patients, 84 had recurrence data, with 52% experiencing tumor recurrence. Age and sex were not significantly different between recurrent and nonrecurrent groups. Nonrecurrent patients had a significantly longer overall survival (54 months vs 35 months, P = .0036). Adjuvant radiation was administered similarly in both groups (25.0% vs 16.2%, P = .4164). There were no differences in capsular or venous invasion or median tumor size. Sixty-two patients had R0 resection and 40.3% (n = 25/62) recurred. Multivariate logistic regression in this cohort, when controlling for vascular invasion, venous invasion, and capsular invasion, revealed that the WNT (odds ratio 4.43 [1.09–18.0], P = .034), PI3K (odds ratio 7.80 [1.33–45.65], P = .023), and cell cycle (odds ratio 6.81 [1.43–32.30], P = .016) pathways were significantly associated with recurrence. Median time to recurrence was 7.9 months; early recurrence (<7.9 months) was associated with MYC pathway alterations (40.9% vs 9.1%, P = .0339). ConclusionThis study identified genomic signatures in the PI3K, WNT, and cell cycle pathways associated with adrenocortical carcinoma recurrence, including in those who underwent R0 resection. Investigations regarding the utility of these signatures as a prognostic tool to dictate adjuvant therapies or targeted treatment are warranted.

7430 Impact Of Environmental Pollution On Adrenocortical Carcinoma In Italy

7430 Impact Of Environmental Pollution On Adrenocortical Carcinoma In Italy

Molecular Subtypes Defined by Cuproptosis-Associated Genes, Prognostic Model Development, and Tumor Immune Microenvironment Characterization in Adrenocortical Carcinoma.

This study aims to explore the role of cuproptosis-related genes in ACC, utilizing data from TCGA and GEO repositories, and to develop a predictive model for patient stratification. A cohort of 123 ACC patients with survival data was analyzed. RNA-seq data of 17 CRGs were examined, and univariate Cox regression identified prognostic CRGs. A cuproptosis-related network was constructed to show interactions between CRGs. Consensus clustering classified ACC into three subtypes, with transcriptional and survival differences assessed by PCA and survival analysis. Gene set variation analysis (GSVA) and ssGSEA evaluated functional and immune infiltration characteristics across subtypes. Differentially expressed genes (DEGs) were identified, and gene clusters were established. A risk score (CRG_score) was generated using LASSO and multivariate Cox regression, validated across datasets. Tumor microenvironment, stem cell index, mutation status, drug sensitivity, and hormone synthesis were examined in relation to the CRG_score. Protein expression of key genes was validated, and functional studies on ASF1B and NDRG4 were performed. Three ACC subtypes were identified with distinct survival outcomes. Subtype B showed the worst prognosis, while subtype C had the best. We identified 214 DEGs linked to cell proliferation and classified patients into three gene clusters, confirming their prognostic value. The CRG_score predicted patient outcomes, with high-risk patients demonstrating worse survival and possible resistance to immunotherapy. Drug sensitivity analysis suggested higher responsiveness to doxorubicin and etoposide in high-risk patients. This study suggests the potential prognostic value of CRGs in ACC. The CRG_score model provides a robust tool for risk stratification, with implications for treatment strategies.

The impact of acyl-CoA:cholesterol transferase (ACAT) inhibitors on biophysical membrane properties depends on membrane lipid composition

Acyl-coenzyme A: cholesterol acyltransferases are enzymes which are involved in the homeostasis of cholesterol. Impaired enzyme activity is associated with the occurrence of various diseases like Alzheimer’s disease, atherosclerosis, and cancers. At present, mitotane is the only inhibitor of this class of enzymes in clinical use for the treatment of adrenocortical carcinoma but associated with common and severe adverse effects. The therapeutic effect of mitotane depends on its interaction with cellular membranes. The search for less toxic but equally effective compounds is hampered by an incomplete understanding of these biophysical properties. In the present study, the interaction of the three ACAT inhibitors nevanimibe, Sandoz 58-035, and AZD 3988 with membranes has been investigated using lipid model membranes in conjunction with biophysical experimental (NMR, ESR, fluorescence) and theoretical (MD simulations) approaches. The data show, that the drugs (i) incorporate into lipid membranes, (ii) differently influence the structure of lipid membranes; (iii) affect membrane structure depending on the lipid composition; and (iv) do not cause hemolysis of red blood cells. The results are discussed with regard to the use of the drugs, in particular to better understand their efficacy and possible side effects.

Robotic lateral resection of inferior vena cava extended to liver segment 7 for adrenocortical carcinoma recurrence (with video)

Robotic lateral resection of inferior vena cava extended to liver segment 7 for adrenocortical carcinoma recurrence (with video)

S4633 Large Adrenocortical Carcinoma Masked as a Liver Mass

S4633 Large Adrenocortical Carcinoma Masked as a Liver Mass

12407 Assessing Human Monocyte Migration And Co-culture With Adrenocortical Cancer Cells

12407 Assessing Human Monocyte Migration And Co-culture With Adrenocortical Cancer Cells

Benign pure androgen-secreting adrenal tumor misdiagnosed as adrenocortical carcinoma on 18F-FDG PET-CT: a rare case report.

Adult pure androgen-secreting adrenal tumors (PASATs) are rarely reported and the malignancy of such tumor are difficult to confirm before surgery. Here we report a PASAT demonstrating extremely 18F-FDG uptake turned out to benign tumor by postoperative pathology examination. A 19-year-old adolescent found a tumor measuring 7.2 cm located in the right adrenal region on enhanced CT during the routine physical examination. Signs of virilization and elevated testosterone and dehydroepiandrosterone (DHEA) were verified during preoperative examination. 18F-FDG PET/CT revealed the tumor had an extremely high 18F-FDG uptake with a SUVmax reaching 42.7, which turned out to be oncocytic adrenocortical adenoma by pathological examination. 18F-FDG PET/CT may be limited in assessing the malignancy of PASAT.

Pseudocysts of the Adrenal Gland: A Systematic Review of Existing Scientific Literature From 2000 to 2023.

Adrenal masses are abnormal growths in the adrenal gland, comprising entities such as pheochromocytomas, adrenal adenomas, adrenocortical carcinomas, and adrenal cysts. Pseudocysts are predominant among adrenal cysts. Due to its infrequent presentation, there are no specific guidelines present in the current literature to steer its management. In such circumstances, a systematic review of the existing literature is imperative to develop comprehensive insights and evidence-based protocols. We aimed to comprehensively analyze the clinico-radiological characteristics and management outcomesof adrenal gland pseudocysts. Human adrenal gland pseudocysts identified through imaging and histopathology, as retrieved from the PubMed search engine, were included in the study. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Joanna Briggs Institute (JBI) CriticalAppraisal Checklist were used to stratify searched studies published between 2000 and 2023. A total of 39 studies were finally included, of which 36 were case reports and three case series, containing 45 patients in total. Data for clinical, radiological, histopathological, and outcome variables were collected, and descriptive analysis was carried out. All cases presented were adults with a clear female predominance of 66.67%. About 26.67% presented with no palpable mass or clinical symptoms, while 28.89% presented with vague abdominal pain. The most prevalent computed tomography (CT) finding was a cystic lesion with calcification and/or hemorrhage and/or necrosis, occurring in 17.78% of cases. Following this, a cystic lesion with only calcification was observed in 13.33% of cases, and a well-defined cystic mass/lesion was found in 11.11% of cases. The most important indication for surgery was compression effect in 44.44%, increasing size in 20.00%, and suspicion of malignancyin another 20.00% of cases. About 64.44% underwent open surgery, while 35.55% underwent minimally invasive surgery. Most patients, 95.55% of the total, had an uneventful postoperative course without any complications. Adrenal gland pseudocyst, though rare and incidental, warrants consideration in differential diagnosis as it presents with vague symptomsand sometimes no symptoms at all. Our review of existing literature highlights the importance of surgical intervention for symptomatic or potentially malignant cysts, with en bloc adrenalectomy being the preferred approach.

Can Psoas muscle density predict the development of metastasis in non-metastatic adrenocortical carcinomas?: A CT-based AI-assisted automated segmentation analysis study

Aim: Our study aimed to investigate whether artificial intelligence-based body composition analysis can predict metastasis development during follow-up in patients with non-metastatic adrenocortical carcinoma (ACC) at the time of diagnosis. Methods: Forty-five patients with non-metastatic ACC were included at the time of diagnosis. From the patients' non-contrast computed tomography (CT) scans, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), psoas area, psoas density, total muscle area, and total muscle density were automatically measured from sections taken at the level of the inferior endplate of the L3 vertebra. Patients were followed for developing liver, lung, and lymph node metastases. The relationship between body composition and liver and lymph node metastasis development was investigated. Propensity score matching (PSM) was performed for patients with metastases. Results: Forty-five patients, 27 of whom were female, with non-metastatic ACC at the time of diagnosis, were included in the study. The mean age of the patients was 53±17.4 years. Significant differences were found between the groups that developed liver metastases and those that did not, and between the groups that developed lymph node metastases and those that did not, in terms of correct Psoas HU, left Psoas HU, PMD, Wall Muscle HU, and age (p

Exophthalmos Revealing Cushing’s Syndrome: A Case Report

Exophthalmos is typically associated with Graves’ ophthalmopathy. Although originally described by Harvey Cushing, exophthalmos is an underappreciated sign of Cushing’s syndrome. We present a case of a patient aged 40 years with no pathological history presenting with generalized asthenia associated with weight loss of 15kg for 2 months, epigastralgia and incoercible vomiting. Clinical examination revealed a normotensive, normocardiac patient with pain on epigastric palpation, bilateral exophthalmos, and an unremarkable cervical examination No cushingoid syndrome especially no facial erythrosis, no purple stretch marks, no buffalo hump, no amyotrophy of the lower limbs. An abdominal CT scan performed before the abdominal pain revealed an adrenal incidentaloma, a right adrenal nodule, well limited, of low density, homogeneous, very discreetly and homogeneously enhanced after injection of contrast medium, whose hemodynamic behavior was in favor of a benign adenoma. The patient underwent surgery for right adrenalectomy, with morphological and immunohistochemical findings in favour of adrenocortical carcinoma, with clinical and biological improvement. We discuss the possible mechanisms causing exophthalmos in patients with either endogenous or exogenous hypercortisolemia.

SURF2 is a MDM2 antagonist in triggering the nucleolar stress response

Cancer cells rely on high ribosome production to sustain their proliferation rate. Many chemotherapies impede ribosome production which is perceived by cells as “nucleolar stress” (NS), triggering p53-dependent and independent pathways leading to cell cycle arrest and/or apoptosis. The 5S ribonucleoprotein (RNP) particle, a sub-ribosomal particle, is instrumental to NS response. Upon ribosome assembly defects, the 5S RNP accumulates as free form. This free form is able to sequester and inhibit MDM2, thus promoting p53 stabilization. To investigate how cancer cells can resist to NS, here we purify free 5S RNP and uncover an interaction partner, SURF2. Functional characterization of SURF2 shows that its depletion increases cellular sensitivity to NS, while its overexpression promotes their resistance to it. Consistently, SURF2 is overexpressed in many cancers and its expression level is an independent marker of prognosis for adrenocortical cancer. Our data demonstrate that SURF2 buffers free 5S RNP particles, and can modulate their activity, paving the way for the research of new molecules that can finely tune the response to nucleolar stress in the framework of cancer therapies.

ClickRNA-PROTAC for Tumor-Selective Protein Degradation and Targeted Cancer Therapy.

Proteolysis-targeting chimeras (PROTACs) show promise in tumor treatment. However, the E3 ligases VHL and CRBN, commonly used in PROTAC, are highly expressed in only a few tumors, thus limiting the application scope and efficacy of PROTAC drugs. Furthermore, the lack of tumor specificity in PROTAC drugs can result in toxic side effects. Therefore, there is an urgent need to develop tumor-selective PROTAC drugs that do not rely on endogenous E3 ligases. In this study, we introduce the ClickRNA-PROTAC system, which involves the expression of a fusion protein of the E3 ubiquitin ligase SIAH1 and SNAPTag through mRNA transfection and recruits the protein of interest (POI) using bio-orthogonal click chemistry. ClickRNA-PROTAC can effectively degrade various proteins such as BRD4, KRAS, and NFκB simply by replacing the warhead molecules. By employing a tumor-specific mRNA-responsive translation strategy, ClickRNA-PROTAC can selectively degrade POIs in tumor cells. Furthermore, ClickRNA-PROTAC demonstrated strong efficacy in targeted cancer therapy in a xenograft mouse model of adrenocortical carcinoma. In conclusion, this approach offers several advantages, including independence from endogenous E3 ubiquitin ligases, tumor specificity, and programmability, thereby paving the way for the development of PROTAC drugs.

Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma.

It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status. In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis. The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%. Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

18F]FDG-PET/CT in adrenal lesions: diagnostic performance in different clinical settings.

Data regarding [18F]FDG-PET/CT for the characterization of adrenal lesions are limited. Most of the studies proposed the tumor-to-liver maximum standardized uptake values (SUVratio) > 1.5 as the best cut off to predict malignancy. The aim of the study was to calculate the optimum cut off in a heterogeneous population with adrenal lesions and evaluate the diagnostic performance SUVratio >1.5. Retrospective analysis of adrenal lesions undergoing [18F]FDG-PET/CT (2013-2022) for different reasons (atypical adrenal incidentalomas, extra adrenal tumor staging). The diagnosis of benignity was assessed by: (i) histology; (ii) stability or minimal diameter increase (<20%/<5 mm) on 12-months follow-up for non-operated patients. The optimal SUVratio and performance of SUVratio >1.5 were calculated by ROC curves. Forty-two consecutive lesions (diameter 36.1 ± 20.3 mm, 6 bilateral) underwent [18F]FDG-PET/CT (19F, age 61.2 ± 11.7 years). Twenty-nine lesions were benign, 11 malignant [8 metastases (2 bilateral) and 1 adrenocortical carcinoma (ACC)] and 2 pheochromocytomas. The SUVratio cut-off in our population was 1.55 (Sn 100%, Sp 73.7%, AUC 0.868), with similar values excluding pheochromocytomas and metastases (SUVratio cut-off 1.49, Sn 100%, Sp 96.3%, AUC 0.988). The SUVratio cut-off of 1.5 showed 100% Sn, 87% Sp, 73% PPV, and 100% NPV. [18F]FDG-PET/CT could help in decision making process avoiding unnecessary surgery. The SUVratio cut-off of 1.5 has a good performance in a heterogenous population.

Cushing's Syndrome: Experience of the Endocrinology Department at University Hospital Center Mohammed VI, Marrakech

Endogenous Cushing's syndrome or endogenous hypercorticism is a rare entity, due to chronic, excessive tissue exposure to glucocorticoids, resulting from excess adrenocorticotropic hormone production or excessive adrenal-autonomous secretion of glucocorticoids. The diagnosis can only be made if the clinical features and biochemical abnormalities are present. Its comorbidities and complications can easily lead to death. Our work is a retrospective descriptive study of all patients with Cushing's syndrome hospitalized in the Endocrinology and Metabolic Diseases Department of the Mohamed VI University Hospital, Marrakech, a total of 34 patients. The aim of this study was to establish the epidemiological, clinical, radiological and etiological profile of Cushing's syndrome observed in the Endocrinology Department of the CHU, and to evaluate the diagnostic modalities, associated parameters and therapeutic management, while comparing them with data in the national and international literature. Our series was characterized by a clear female predominance (4/1) and an average age of 29.2 years. Discovery followed weight gain in 53% of patients, headache in 35%, hirsutism and secondary amenorrhea in 32% and 29% respectively. The most common clinical signs were hypercorticism in 71% of cases and hyperandrogenism in 59%. Biologically, to detect hypercorticism, dexamethasone minute braking was performed in 65% of cases. ACTH dependence was found in 91% of cases, with Cushing's disease found in 53% of cases, diagnosed on MRI, with a microadenoma in 65% of cases. Among the causes of ACTH Independence, adrenocortical carcinomas were found on adrenal CT in 25% of cases, and adenomas in 31.2%. From a therapeutic point of view, surgery took first place in these cases: trans-sphenoidal adenomectomy for adrenocortical adenomas and adrenalectomy for adrenal tumors. Adrenalectomy was also indicated in two cases of ACTH-dependent hypercorticism (Cushing's disease and paraneoplastic) ......

Hyperthermia-induced cell death in adrenocortical carcinoma: efficacy and mechanisms beyond caspase 3 apoptosis

Hyperthermia-induced cell death in adrenocortical carcinoma: efficacy and mechanisms beyond caspase 3 apoptosis

IGF-2 mediated hypoglycemia in adrenocortical carcinoma: a case series

IGF-2 mediated hypoglycemia in adrenocortical carcinoma: a case series

Uptake of K20-coated iron oxide nanoparticles by adrenocortical carcinoma cells

Uptake of K20-coated iron oxide nanoparticles by adrenocortical carcinoma cells

Management and outcomes of patients treated with mitotane for adrenocortical carcinoma in a tertiary adrenal tumour centre in Ireland

Management and outcomes of patients treated with mitotane for adrenocortical carcinoma in a tertiary adrenal tumour centre in Ireland