Adrenocortical Carcinoma Research Articles

Comparison oPf 68Ga-FAPI and 18F-FDG PET/CT Findings in Oncocytic and Conventional Subtypes of Pediatric Adrenocortical Carcinoma.

Adrenocortical carcinoma, a poor prognosis cancer with a low survival rate, is a rare pediatric malignancy. We performed 18F-FDG PET/CT and 68Ga-FAPI PET/CT imaging in 2 children with different subtypes of adrenocortical carcinoma and compared the findings. FAPI PET/CT revealed superior performance in patient with conventional subtype and in detecting skeletal lesions. However, the recurrent lesions in the surgical bed had higher FDG uptake in both patients.

Digenic Inheritance of Monoallelic MUTYH and POLE Germline Variants in Adrenocortical Carcinoma: Implications for Tumorigenesis and Immunotherapy.

Collision of monoallelic MUTYH and POLE germline variants in a patient with adrenocortical carcinoma who achieved a strong response to immunotherapy.

Up-regulated DDX39 in Adrenocortical Carcinoma Is Associated With Patient Survival.

Adrenocortical carcinoma is a very rare tumor characterized by poor prognosis and high mortality. The origin of this tumor is primarily the adrenal cortex. The 5-year overall survival rate of patients with adrenocortical carcinoma has not improved despite therapeutic advances. Early detection of this malignancy remains difficult, and no standard curative therapy currently exists. Therefore, it is important to understand the biology of adrenocortical carcinoma, and to identify prognostic biomarkers and molecular targets for its therapy. DDX39 is an Asp-Glu-Ala-Asp (DEAD)-box RNA helicase, which is required for transcription, splicing and transport of mRNA. There are some reports about overexpression of DDX39 in tumor tissues and cells (lung squamous cell cancer, gastrointestinal stromal tumor, urinary bladder cancer, malignant pleural mesothelioma). However, the clinicopathological involvement of DDX39 in adrenocortical carcinoma has not yet been documented. The GEPIA, GEPIA2, and UALCAN platforms were used to analyze DDX39 mRNA expression and survival in patients with adrenocortical carcinoma. DDX39 was found to be significantly up-regulated in adrenocortical carcinoma tissues, and this up-regulation inversely correlated with prolonged patient survival. DDX39 may be a potential prognostic biomarker in patients with adrenocortical carcinoma.

A first-in-human phase I trial with antibody drug conjugate ADCT-701 in neuroendocrine tumors and carcinomas.

TPS672 Background: Neuroendocrine neoplasms (NENs) consist of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which are rare malignancies found in various anatomical sites, including the gastrointestinal tract, pancreatic islets, lungs, and adrenal glands. Poorly differentiated NECs are classified as high-grade carcinomas that bear resemblance to small-cell lung cancer (SCLC). Treatment for poorly differentiated NECs typically follows small-cell carcinoma guidelines, utilizing platinum-based regimens; however, these patients experience a high risk of relapse and demonstrate a limited response to additional systemic therapies. Adrenocortical carcinoma (ACC) is another rare malignancy associated with a median survival of approximately 14.5 months post-diagnosis, and advanced disease management options show limited efficacy. Currently, no targeted therapies have demonstrated significant effectiveness for this condition. Preclinical investigations have indicated that Delta-like non-canonical notch ligand 1 (DLK1) is expressed in various neuroendocrine neoplasms, including ACC, SCLC, neuroblastoma, pheochromocytoma, and paraganglioma. ADCT-701, a humanized antibody targeting DLK1, has shown potential in suppressing tumor growth and enhancing survival across multiple cancer models expressing this marker. Methods: This Phase I dose escalation study (NCT06041516) aims to enroll adult patients with histologically or cytologically confirmed neuroendocrine neoplasms or malignant ACC with evaluable disease, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants will be part of a dose-finding trial. A 3+3 design is utilized to assess up to ten different dose levels of ADCT-701. Dose escalation continues unless dose-limiting toxicities occur, the maximum tolerated dose (MTD) is reached, or an optimal dose is established. The primary endpoint of the study is to ascertain the recommended phase 2 dose of ADCT-701 in patients with neuroendocrine neoplasms or malignant adrenocortical carcinoma. Secondary endpoints will assess safety, preliminary tumor activity, response rate, overall survival, pharmacokinetics, and the immunogenicity profile of ADCT-701. The trial aims to enroll up to 70 evaluable patients across a maximum of 10 dose levels. For further details, please refer to clinical trial information NCT06041516. Clinical trial information: NCT06041516 .

Whole Genome Profiling of Primary and Metastatic Adrenocortical Carcinoma Unravels Significant Molecular Events

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with limited treatment options and poor prognosis, with a 5-year survival rate of about 15 %. This study used whole genome sequencing to characterize the genomic landscape of five patients, one of them with both primary and metastatic samples. Key driver mutations were detected, including APC, JAK1, RFWD3 as well as other genes. Notably, a primary tumor harbored a RAD51 biallelic deleterious translocation, associated with homologous recombination deficiency signature. Large-scale copy neutral loss of heterozygosity (LOH) was identified in four tumors, three had TP53 mutations, with structural variants impacting genes as RB1, CDKN2A, and NF1. A genomic signature specific to mismatch repair was observed in a sample with MHS6 mutation. Two tumors presented novel fusions at TERT locus, including TERT::ZNF521. Comparative analysis between conventional and oncocytic ACC subtypes revealed no significant differences in mutation load, microsatellite instability, or specific gene enrichment. This comprehensive WGS analysis broadens the spectrum of genomic alterations in ACC, highlighting potential molecular targets and differences across subtypes that may inform future therapeutic strategies.

Prognostic value of total, free and lipoprotein fraction-bound plasma mitotane levels in advanced adrenocortical carcinoma: a prospective study of the ENDOCAN-COMETE-Cancer network.

Mitotane is the only approved treatment for metastatic adrenocortical carcinoma (ACC). Monitoring plasma levels is recommended, but its predictive value is insufficient. This prospective study of the French ENDOCAN-COMETE network aimed to investigate the prognostic role of plasma mitotane levels pharmacokinetics and free or bound to lipoprotein fraction measurements during six consecutive months. Lipoprotein fractions were isolated by ultracentrifugation, and mitotane level was determined by HPLC-UV. Total, free, and lipoprotein fraction bound plasma mitotane were monitored every two months for six months with morphological assessment. The primary endpoint was overall survival (OS). 21 patients with metastatic ACC were included. Median overall survival was 23months. The median free mitotane level per patient was 12% (± 7%), and the majority (88%) was bound to lipoprotein fractions. Several pharmacokinetics measures of total mitotane were related to OS: first level at one month (p = 0.026), mean level (p = 0.055), and area under the curve (AUC) (p = 0.048), with higher exposure associated to longer OS. Free mitotane (not bounded) and mitotane bounded to lipoprotein subfraction added no prognostic values. The relationship between the mitotane level and OS suggested a minimum "effective" threshold of 10-15mg/L or an area under the curve above 100mg/L/month with no individualized maximum value. This prospective study did not identify any added prognostic value of free mitotane level over the total level. Early total mitotane level measurements (before 3-6months) were related to OS with a higher and faster exposure related to more prolonged survival.

Prognostic relevance of AGO2 expression in adrenocortical carcinoma (ACC): associations with clinicopathological features

Prognostic relevance of AGO2 expression in adrenocortical carcinoma (ACC): associations with clinicopathological features

833 A rare case of metastatic adrenal cortical carcinoma in a patient missed follow up for adrenal nodule

833 A rare case of metastatic adrenal cortical carcinoma in a patient missed follow up for adrenal nodule

Rethinking the definition of stage III disease in adrenocortical carcinoma: Assessing the impact of clinical lymph node positive disease.

Stage III adrenocortical carcinoma encompasses both lymph node positive (TanyN1M0) and negative (T3-4N0M0) disease. Given the disease's rarity, the current staging paradigm's estimates of survival are supported by limited evidence. Consequently, we examined the impact of clinical lymph node positivity on survival outcomes in the context of the current staging of advanced adrenocortical carcinoma. We identified patients with clinical stage III and IV disease from the National Cancer Database. Kaplan-Meier methods and Cox proportional hazards models estimated overall survival for stage III lymph node negative, stage III lymph node positive, and stage IV disease. We identified 917 patients with adrenocortical carcinoma - 322 (35.1%) stage III lymph node negative, 67 (7.3%) stage III lymph node positive, and 528 (57.6%) stage IV. 3-year overall survival for patients with stage III lymph node negative, stage III lymph node positive, and stage IV disease was 48.6%, 29.4%, and 15.6%, respectively. On univariable analysis, patients with stage III lymph node positive disease were associated with worse survival than those with stage III lymph node negative disease (HR 1.72, 95% CI 1.26-2.37, P < 0.001); however, this relationship did not maintain significance in multivariable analysis (HR 1.27, 95% CI 0.88-1.83, P = 0.21). Our study finds that patients with clinical stage III lymph node positive adrenocortical carcinoma may have worse survival outcomes than stage III patients without lymph node involvement. The results of this study suggest the need for an updated, more nuanced staging paradigm, which differentiates stage III disease by lymph node positivity.

The differential diagnosis of adrenocortical tumors: systematic review of Ki-67 and IGF2 and meta-analysis of Ki-67.

Distinguishing benign from malignant adrenocortical tumors (ACT) is not always easy, particularly for tumors with unclear malignant potential based on the histopathological features comprised of the Weiss score. Previous studies reported the potential utility of immunohistochemistry (IHC) markers to recognize malignancy, in particular the Insulin-like growth factor 2 (IGF2) and the proliferation marker, Ki-67. However, this information was not compiled before. Therefore, this review aimed to collect the evidence on the potential diagnosis utility of IGF2 and Ki-67 IHC staining. Additionally, a meta-analysis was performed to assess the Ki-67 accuracy to identify adrenocortical carcinoma. The systematic review and meta-analysis were conducted according to the PRISMA guidelines. From the 26 articles included in the systematic review, 21 articles provided individual data for IGF2 (n = 2) or for Ki-67 (n = 19), while 5 studies assessed both markers. IGF2 staining was positive in most carcinomas, in contrast to adenomas. However, the different immunostaining evaluation methods adopted among the studies impeded to perform a meta-analysis to assess IGF2 diagnostic accuracy. In contrast, for the most commonly used cut-off value of 5% stained cells, Ki-67 showed pooled specificity, sensitivity and log diagnostic odds ratio of 0.98 (95% CI 0.95 to 0.99), 0.82 (95% CI 0.65 to 0.92) and 4.26 (95% CI 3.40 to 5.12), respectively. At the 5% cut-off, Ki-67 demonstrated an excellent specificity to recognize malignant ACT. However. the moderate sensitivity observed indicates the need for further studies exploring alternative threshold values. Additionally, more studies using similar approaches are needed to assess the diagnostic accuracy of IGF2.Registration code in PROSPERO: CRD42022370389.

Minimally invasive adrenalectomy for adrenocortical cancers: A systematic review

Minimally invasive adrenalectomy for adrenocortical cancers: A systematic review

P-04 A PATIENT WITH A GIANT ADRENAL MASS DETECTED DURING PREGNANCY

Abstract Introduction Although the frequency of adrenal incidentalomas is increasing, they are rarely detected due to lack of imaging during pregnancy. Here, we present a case of adrenal incidentaloma diagnosed during pregnancy. Clinical Case A 32-year-old female patient was diagnosed with a mass in the liver during obstetric ultrasonography performed in the 4th month of pregnancy and was referred to gastroenterology clinic for further examination, but any additional intervention could not be made because of patient’s refusion. She underwent an emergent caesarean section at 36th weeks of pregnancy. A mass approximately 15 cm in size, thought to be of adrenal origin, was detected in the retroperitoneal area posterior to the liver at the surgery. Abdominal MRI revealed a 188*121*113 mm non-adenomatous lesion, at right adrenal gland, containing cystic necrotic areas, and not suppressed in fat-suppressed series (figure 1A). At initial assesment by endocrinology, the patient denied any paroxysmal or persistent hypertension, weakness, weight gain and hirsutism. Physical examination was found normal, no signs of Cushing’s syndrome was observed. Laboratory testing including 24-hour urine catecholamines, basal cortisol, dehydroepiandrosterone sulfate (DHEA-S), adrenocorticotropic hormone (ACTH) were in reference ranges. The cortisol levels were supressed following the low-dose dexamethasone test. Adrenal carcinoma was suspected based to radiological features of the lesion. FDG uptake of the mass with a SUVmax: 16.9 was reported at PET-scan (figure 1B). Laparotomy for right adrenal gland was planned, but the patient disapproved once again. She underwent to adrenalectomy 18 months later after the mass was detected. Surprisingly, the pathology resulted as adrenocortical adenoma. Ki67 labeling index was found to be 3-4%, immunohistochemical staining of tissue specimens showed that synaptophysin and chromogranin A negative ( - ), but CD56 positive (++). The patient was lost for approximately 1 year and then aplied to our clinic with another unplanned pregnancy. She is doing well at the 32nd week of her second pregnancy. Conclusion Large and non-adenomatous masses detected during pregnancy are likely to be malignant and these masses are usually known with poor-prognosis. Rarely, as seen in our patient, huge adrenal masses may exhibit a benign behavior compatible with an uncomplicated long process despite suspicious radiological imaging features.Figure 1A:Abdominal MRI revealed a 188*121*113 mm non-adenomatous lesion, at right adrenal gland containing cystic necrotic areas. B:Increased uptake of FDG in the right adrenal region (SUVmax: 16.9)

Clinical presentation, management, and outcomes of patients with small (≤ 4 cm) adrenocortical carcinoma: single-center retrospective cohort study

Clinical presentation, management, and outcomes of patients with small (≤ 4 cm) adrenocortical carcinoma: single-center retrospective cohort study

Silent adrenal neoplasm masquerading as adrenocortical carcinoma in a patient with neurofibromatosis type 1

Silent adrenal neoplasm masquerading as adrenocortical carcinoma in a patient with neurofibromatosis type 1

Cross-study reconciliation of SF-1 regulatory targets in adrenocortical carcinoma through in silico analysis

Cross-study reconciliation of SF-1 regulatory targets in adrenocortical carcinoma through in silico analysis

In vivo CRISPR screening identifies tada2b as a key epigenetic regulator of immune response in adrenocortical carcinoma

<i>In vivo</i> CRISPR screening identifies tada2b as a key epigenetic regulator of immune response in adrenocortical carcinoma

Clinical and genetic characteristics of patients with adrenocortical carcinoma and lynch syndrome

Clinical and genetic characteristics of patients with adrenocortical carcinoma and lynch syndrome

PCDHGC3 hypermethylation as a diagnostic and prognostic biomarker in adrenocortical carcinomas

PCDHGC3 hypermethylation as a diagnostic and prognostic biomarker in adrenocortical carcinomas

Outcome of combination chemotherapy for metastatic adrenocortical carcinoma

Outcome of combination chemotherapy for metastatic adrenocortical carcinoma

Evaluating the response of immunotherapy in metastatic adrenocortical carcinoma - a single institution retrospective review

Evaluating the response of immunotherapy in metastatic adrenocortical carcinoma - a single institution retrospective review