H-score of 11β-hydroxylase and aldosterone synthase in the histopathological diagnosis of adrenocortical tumors. Yang Yi,Xiao Ming,Song Ying,Tang Yi,Luo Ting,Yang Shumin,He Wenwen,Cheng Qingfeng,Ma Linqiang,Zhang Yao,He Yunfeng,Cao Youde,Yang Jun,Peng Bin,Hu Jinbo,Li Qifu Endocrine PURPOSE:To assess the diagnostic performance of the H-score of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in the histopathological diagnosis of adrenocortical tumors (ACT). METHODS:We retrospectively evaluated 199 cases of ACT, of which 85 were diagnosed as aldosterone-producing adenoma (APA), 66 as cortisol-producing adenoma (CPA), 9 as aldosterone-cortisol co-secreting adenoma, 30 as nonhyperfunctioning adenoma, and 9 as adrenocortical carcinoma (ACC). Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies. The staining was quantified by the McCarty's H-score system. The diagnostic performance was assessed by the receiver operating characteristic curve (ROC). RESULTS:The H-score of CYP11B1 is highest in the CPA group and lowest in the ACC group. The H-score of CYP11B2 in the APA group is significantly higher than other ACT groups. The area under ROC (AUC) of an increased H-score of CYP11B2 (>65) for the diagnosis of APA was 0.971 (95%CI 0.937-0.990). The AUC of an increased H-score of CYP11B1 (>204) for the diagnosis of CPA was 0.725 (95%CI 0.658-0.786). The AUC of a decreased H-score of CYP11B1 (<85) for the diagnosis of ACC was 0.960 (95%CI 0.923-0.983). CONCLUSIONS:H-score of CYP11B1 and CYP11B2 are reliable tools for the histopathological subtyping of functional benign ACT and may offer some value in the histopathological diagnosis of malignant ACT. 10.1007/s12020-019-02022-8

Advances in translational research of the rare cancer type adrenocortical carcinoma. Nature reviews. Cancer Adrenocortical carcinoma is a rare malignancy with an annual worldwide incidence of 1-2 cases per 1 million and a 5-year survival rate of <60%. Although adrenocortical carcinoma is rare, such rare cancers account for approximately one third of patients diagnosed with cancer annually. In the past decade, there have been considerable advances in understanding the molecular basis of adrenocortical carcinoma. The genetic events associated with adrenocortical carcinoma in adults are distinct from those of paediatric cases, which are often associated with germline or somatic TP53 mutations and have a better prognosis. In adult primary adrenocortical carcinoma, the main somatic genetic alterations occur in genes that encode proteins involved in the WNT-β-catenin pathway, cell cycle and p53 apoptosis pathway, chromatin remodelling and telomere maintenance pathway, cAMP-protein kinase A (PKA) pathway or DNA transcription and RNA translation pathways. Recently, integrated molecular studies of adrenocortical carcinomas, which have characterized somatic mutations and the methylome as well as gene and microRNA expression profiles, have led to a molecular classification of these tumours that can predict prognosis and have helped to identify new therapeutic targets. In this Review, we summarize these recent translational research advances in adrenocortical carcinoma, which it is hoped could lead to improved patient diagnosis, treatment and outcome. 10.1038/s41568-023-00623-0

Adrenocortical carcinoma: Diagnosis, prognostic classification and treatment of localized and advanced disease. Cancer treatment and research communications Adrenocortical carcinoma (ACC) is a rare cancer with an estimated incidence of 0.7 to 2.0 cases per 1 million population per year in the United States. It is an aggressive cancer originating in the cortex of the adrenal gland with a poor prognosis. The 5-year survival rate is less than 15% among patients with metastatic disease. In this article, we review the epidemiology and pathogenesis of ACC, the diagnostic procedures, the prognostic classification of ACC, and the treatment options from localized and resectable forms to advanced disease detailing recent therapeutic developments such as immunotherapy and molecularly targeted therapy. 10.1016/j.ctarc.2023.100759

Adrenocortical carcinoma: a literature review. Thampi Ammu,Shah Ekta,Elshimy Ghada,Correa Ricardo Translational cancer research Adrenocortical carcinoma (ACC) is reported to be present in 3-10% of the population with most tumors presenting as benign tumors. Most cases of ACC are a sporadic accumulation of mutations over time. However, studies show a predisposition to various genetic mutations may contribute. Research over the last couple of decades has elucidated causes of ACC to be driven by several molecular changes that include inactivation of tumor suppressor genes and activation of a myriad of different oncogenes, DNA mutations, and epigenetic changes. The widely adopted staging of ACC is by European Network of Study of Adrenal Tumors (ENSAT) due to its correlations with clinical outcomes. At the time of presentation, a detailed history taking with attention to the history of symptoms of hormonal excess and family history of possible hereditary influence is the first step of evaluation. It is followed by a thorough physical examination for evaluation of ACC. Management of ACC poses a unique challenge as it involves oncologic and endocrine issues. Except for one trial, treatment guidelines are based on retrospective studies and non-randomized trials, and therefore the level of evidence is grade II to grade IV. Personalized therapy including identifying the actionable target in each patient is the future of ACC management. The knowledge base of ACC is evolving based on the basic science and clinical trials conducted by worldwide groups such as COMITE of France, ENSAT of Europe, TCGA project and American Australian Asian Adrenal Alliance (A5). Future studies should aim at clear molecular and clinical standardization. Recommended therapeutic strategies should be prospectively recorded. 10.21037/tcr.2019.12.28

Adrenocortical carcinoma: the range of appearances on CT and MRI. Bharwani Nishat,Rockall Andrea G,Sahdev Anju,Gueorguiev Maria,Drake William,Grossman Ashley B,Reznek Rodney H AJR. American journal of roentgenology OBJECTIVE:Adrenocortical carcinoma (ACC) is a rare, aggressive tumor arising from the adrenal cortex that typically presents late with a large mass. The increased use of cross-sectional imaging for unrelated reasons has led to a greater number of ACCs being detected incidentally at an earlier stage. Recognition of the typical clinical, biochemical, and imaging findings is imperative for rapid diagnosis, prompt intervention, and early use of the appropriate therapy. CONCLUSION:Cross-sectional imaging with CT and MRI is essential for determining the extent of local and distant tumor spread. Complete surgical resection is currently the only potentially curative treatment of ACC, and the information attained from CT and MRI is important to guide surgery and further patient management. 10.2214/AJR.10.5540