scholarly journals Pathobiology and genetics of adrenocortical carcinoma

2019 ◽  
Vol 62 (2) ◽  
pp. R105-R119 ◽  
Author(s):  
James F H Pittaway ◽  
Leonardo Guasti
Keyword(s):  
Adrenal Cortex ◽  
Adjuvant Treatment ◽  
Adrenocortical Carcinoma ◽  
Genetic Alterations ◽  
High Recurrence Rate ◽  
Self Renewal ◽  
Steroidogenic Cells ◽  
Rare Malignancy ◽  
Definition Of ◽  
Stem Cell Hierarchy

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence worldwide of 0.7–2.0 cases/million/year. Initial staging is the most important factor in determining prognosis. If diagnosed early, complete surgical resection +/− adjuvant treatment can lead to 5-year survival of up to 80%. However, often it is diagnosed late and in advanced disease, 5-year survival is <15% with a high recurrence rate even after radical surgery. The mainstay of adjuvant treatment is with the drug mitotane. Mitotane has a specific cytotoxic effect on steroidogenic cells of the adrenal cortex, but despite this, progression through treatment is common. Developments in genetic analysis in the form of next-generation sequencing, aided by bioinformatics, have enabled high-throughput molecular characterisation of these tumours. This, in addition to a better appreciation of the processes of physiological, homeostatic self-renewal of the adrenal cortex, has furthered our understanding of the pathogenesis of this malignancy. In this review, we have detailed the pathobiology and genetic alterations in adrenocortical carcinoma by integrating current understanding of homeostasis and self-renewal in the normal adrenal cortex with molecular profiling of tumours from recent genetic analyses. Improved understanding of the mechanisms involved in self-renewal and stem cell hierarchy in normal human adrenal cortices, together with the identification of cell populations likely to be co-opted by oncogenic mutations, will enable further progress in the definition of the molecular pathways involved in the pathogenesis of ACC. The combination of these advances eventually will lead to the development of novel, effective and personalised strategies to eradicate molecularly annotated ACCs.

Virilizing Adrenocortical Carcinoma Resected With Negative Margins Treated With Surgery Alone

2021 ◽  
pp. 000313482110508
Author(s):  
Tyler Fields ◽  
Kelsee Felux ◽  
Alejandro Chavarriaga ◽  
Philip Ramsay ◽  
Evan Weitman
Keyword(s):  
Menstrual Cycle ◽  
Adjuvant Treatment ◽  
Adrenocortical Carcinoma ◽  
Rare Case ◽  
Physical Exam ◽  
Rare Malignancy ◽  
Uncommon Tumor

Adrenocortical carcinoma is a rare malignancy. A virilizing adrenocortical carcinoma is even more unique of a diagnosis. In this report, we present a rare case of this uncommon tumor with an interesting presentation, clearly documented physical exam changes over a span of at least 8 years, and a technically challenging case. We also briefly review the management of adrenocortical carcinoma. The tumor was successfully resected with no planned adjuvant treatment at this time. The patient had recurrence of menstrual cycle post-operatively and required no steroid supplementation.

scholarly journals Paediatric Nonfunctioning Adrenocortical Carcinoma with Extension up to Right-Side Heart: Cardiac Surgery Approach

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Federica Iezzi ◽  
Andrea Quarti ◽  
Chiara Surace ◽  
Marco Pozzi
Keyword(s):  
Cardiac Surgery ◽  
Adrenal Gland ◽  
Adjuvant Treatment ◽  
Adrenocortical Carcinoma ◽  
Rare Case ◽  
Cardiac Involvement ◽  
Adrenal Carcinoma ◽  
Rare Malignancy ◽  
The Right ◽  
Treatment Prognosis

Adrenocortical carcinoma is a rare malignancy. Due to late diagnosis and no adequate effective adjuvant treatment, prognosis remains poor. Only approximately 30% of these malignancies are confined to the adrenal gland when they are diagnosed, as these tumors tend to be found years after their genesis. Cardiac involvement of adrenal carcinoma is very rare. We report a rare case of a 7-year-old female with right adrenal cortical carcinoma, involving the right-side heart.

scholarly journals Case Report: Ectopic Adrenocortical Carcinoma in the Ovary

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen-Hsuan Tsai ◽  
Tze-Chien Chen ◽  
Shuen-Han Dai ◽  
Yi-Hong Zeng
Keyword(s):  
Adrenocortical Carcinoma ◽  
Performance Status ◽  
Poor Performance ◽  
Abdominal Circumference ◽  
Poor Performance Status ◽  
Test Results ◽  
Ki 67 ◽  
Complete Survey ◽  
Rare Malignancy ◽  
Captopril Test

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/million habitants/year. ACCs are rare and usually endocrinologically functional. We present the case of a 59-year-old woman who experienced abdominal fullness for 6 months and increased abdominal circumference. A large pelvic tumor was observed. She underwent cytoreductive surgery and the pathological test results revealed local tumor necrosis and prominent lympho-vascular invasion. Neuroendocrine carcinoma was the first impression, but positivity for synaptophysin, alpha-inhibin, transcription factor enhancer 3 (TFE-3), calretinin (focal), and CD56 (focal) and high Ki-67-labeling proliferating index (&gt;80%) confirmed the diagnosis of ectopic ACC. Ectopic primary aldosteronism could not be excluded. However, we did not perform saline infusion test or captopril test due to poor performance status. When pathological test reports reveal neuroendocrine features not typically found in the organ being examined, IHC staining should be performed to rule out ectopic ACC. Whether the ectopic ACC is functional or not requires complete survey.

Molecular defects in thyroid carcinomas: Role of the RET oncogene in thyroid neoplastic transformation

1995 ◽  
Vol 133 (5) ◽  
pp. 513-522 ◽  
Author(s):  
Massimo Santoro ◽  
Michele Grieco ◽  
Rosa Marina Melillo ◽  
Alfredo Fusco ◽  
Giancarlo Vecchio
Keyword(s):  
Tyrosine Kinases ◽  
Point Mutations ◽  
Neoplastic Transformation ◽  
Thyroid Neoplasms ◽  
Genetic Alterations ◽  
Thyroid Carcinomas ◽  
Molecular Defects ◽  
Genetic And Environmental Factors ◽  
Definition Of

Santoro M, Grieco M, Melillo RM, Fusco A, Vecchio G. Molecular defects in thyroid carcinomas. Role of the RET oncogene in thyroid neoplastic transformation. Eur J Endocrinol 1995;133:513–22. ISSN 0804–4643 Tumors are believed to arise as a result of an accumulation of mutations in critical genes involved in the control of cell proliferation. Thyroid neoplasms represent a good model for studying the role of these mutations in epithelial cell multistep carcinogenesis because they comprise a broad spectrum of lesions with different degrees of malignancy. Recent reports have described the involvement of specific genetic alterations in different types of thyroid neoplasms. Papillary carcinomas are characterized by the activation of the receptor tyrosine kinases RET and TRK-A proto-oncogenes. Ras point mutations are frequently observed in tumors with follicular histology and a high prevalence of p53 point mutations have been found in anaplastic carcinomas. A definition of molecular defects characterizing thyroid tumors will be helpful in establishing sensitive and specific detection strategies and, in addition, to define genetic and environmental factors important for their pathogenesis. Giancarlo Vecchio, Dipartimento di Biologia e Patologia Cellulare e Molecolare "L, Califano", Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli "Federico II", via S Pansini 5, 80131 Napoli, Italy

scholarly journals Adjuvant Radiation Improves Recurrence-Free Survival and Overall Survival in Adrenocortical Carcinoma

2019 ◽  
Vol 104 (9) ◽  
pp. 3743-3750 ◽  
Author(s):  
Laila A Gharzai ◽  
Michael D Green ◽  
Kent A Griffith ◽  
Tobias Else ◽  
Charles S Mayo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adrenocortical Carcinoma ◽  
Adjuvant Radiation ◽  
Recurrence Free Survival ◽  
University Of Michigan ◽  
Free Survival ◽  
Tumor Bed ◽  
Distant Failure ◽  
Rare Malignancy ◽  
The University

Abstract Context Adrenocortical carcinoma (ACC) is a rare malignancy with high rates of recurrence and poor prognosis. The role of radiotherapy (RT) in localized ACC has been controversial, and RT is not routinely offered. Objective To evaluate the benefit of adjuvant RT on outcomes in ACC. Design This is a retrospective propensity-matched analysis. Setting All patients were seen through the University of Michigan’s Endocrine Oncology program, and all those who underwent RT were treated at the University of Michigan. Participants Of 424 patients with ACC, 78 were selected; 39 patients underwent adjuvant radiation. Intervention Adjuvant RT to the tumor bed and adjacent lymph nodes. Main Outcomes Measures Time to local failure, distant failure, or death. Results Median follow-up time was 4.21 years (95% CI, 2.79 to 4.94). The median radiation dose was 55 Gy (range, 45 to 60). The 3-year overall survival estimate for patients improved from 48.6% for patients without RT (95% CI, 29.7 to 65.2) to 77.7% (95% CI, 56.3 to 89.5) with RT, with a hazard ratio (HR) of 3.59 (95% CI, 1.60 to 8.09; P = 0.002). RT improved local recurrence-free survival (RFS) from 34.2% (95% CI, 18.8 to 50.3) to 59.5% (95% CI, 39.0 to 75.0), with an HR of 2.67 (95% CI, 1.38 to 5.19; P = 0.0035). RT improved all RFS from 18.3% (95% CI, 6.7 to 34.3) to 46.7% (95% CI, 26.9 to 64.3), with an HR 2.59 (95% CI, 1.40 to 4.79; P = 0.0024). Conclusions In the largest single institution study to date, adjuvant RT after gross resection of ACC improved local RFS, all RFS, and overall survival in this propensity-matched analysis. Adjuvant RT should be considered a part of multidisciplinary management for patients with ACC.

scholarly journals Functioning Adrenocortical Carcinoma with Extension upto the Right Atrium Producing Cushing's Syndrome

2013 ◽  
Vol 3 ◽  
pp. 32 ◽  
Author(s):  
Santosh Kumar ◽  
Gautam R. Choudhary ◽  
Arawat Pushkarna
Keyword(s):  
Inferior Vena Cava ◽  
Cushing’S Syndrome ◽  
Adrenocortical Carcinoma ◽  
Right Atrium ◽  
Inferior Vena ◽  
Vena Cava ◽  
Cushing's Syndrome ◽  
Curative Therapy ◽  
Rare Malignancy ◽  
The Right

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Surgery is the only curative therapy available and overall 5-year survival for patients who undergo a complete resection is 32% to 48%. They are known to produce intravascular invasion and into the inferior vena cava (IVC) and in rare cases they may reach the right atrium. We report a case of functioning ACC extending into the inferior vena cava and right atrium in a female with Cushing's syndrome.

scholarly journals GENE-14. BMP4 INDUCES TO ASYMMETRIC CELL DIVISION IN HUMAN GLIOMA STEM-LIKE CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi100-vi100
Author(s):  
Motofumi Koguch ◽  
Hideki Izumi ◽  
Yukiko Nakahara ◽  
Hiroshi Ito ◽  
Tomihiro Wakamiya ◽  
...  
Keyword(s):  
Cell Division ◽  
Asymmetric Cell Division ◽  
Malignant Tumors ◽  
Treatment Resistance ◽  
Stem Cell Marker ◽  
Immunofluorescent Staining ◽  
High Recurrence Rate ◽  
Self Renewal ◽  
Tumor Sphere ◽  
New Perspective

Abstract Glioblastoma (GBM) is one of the human malignant tumors with a high recurrence rate and the poorest prognosis. Therefore, a new treatment strategy is required. It has also come to be thought that cancer is a heterogeneous, which composes of cancer stem cells (CSCs), which have self-renewal ability, multipotency and treatment resistance. Although various strategies targeting glioma stem-like cells (GSCs) have been studied, a median survival remains to be less than 2 years. In this study, we focused on strategies targeting GSCs through induction of differentiation using BMP4. We examined the expression of CD133, a cancer stem cell marker, under BMP4-treatment in GSCs using flowcytometry analysis, western blotting and qPCR. We also examined immunofluorescent staining of GSCs to study cell division. The treatment of BMP4 caused downregulation of CD133 expression in GSCs. In addition, BMP4-treatment induced to asymmetric cell division in GSCs. Tumor sphere assay showed that BMP4 suppresses self-renewal ability. These findings may provide a new perspective how BMP4 reduces the tumorigenicity of GSCs.

ETO2-GLIS2 Controls Differentiation Arrest and Self-Renewal through Aberrant Enhancers Regulation in Pediatric Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 572-572
Author(s):  
Cecile Thirant ◽  
Cecile K Lopez ◽  
Cathy Ignacimouttou ◽  
M'Boyba Diop ◽  
Lou Le Mouël ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Genetic Alterations ◽  
Leukemic Cells ◽  
Hematopoietic Progenitors ◽  
Pediatric Leukemia ◽  
Self Renewal ◽  
Megakaryocytic Differentiation ◽  
Acute Myeloid

Abstract Deregulated gene expression due to genetic alterations, such as gene fusions affecting transcription and/or epigenetic factors is the hallmark of acute myeloid leukemia and the basis for the differentiation block of hematopoietic progenitors. Acute megakaryoblastic leukemia (AMKL) is a subtype of poor prognosis acute myeloid leukemia (AML) affecting primarily young children. Recently, the ETO2-GLIS2 fusion has been identified in 20-30% of de novo AMKL and associated with the worst prognosis in this subtype of AML. To characterize the transformation induced by ETO2-GLIS2, we first defined the consequences of ETO2-GLIS2 expression on hematopoietic progenitors and the contribution of ETO2 and GLIS2 on differentiation and self-renewal. Using methylcellulose replating assays and phenotype characterization, we show that the GLIS2 moiety drives the megakaryocytic phenotype whereas both the ETO2 and GLIS2 moieties are required for maintaining self-renewal. Global expression profiling and comparison to patients' signature consistently identify ETO2-GLIS2-mediated deregulation of major transcriptional regulators of hematopoiesis and leukemogenesis, including overexpression of the ERG oncogene. ChIP-seq analysis reveals that ETO2-GLIS2 is recruited at normal ETO2 complexes sites and also at GLIS2-specific targets through binding via GLIS2 DNA-binding domain. We demonstrate that ETO2-GLIS2 fusion localize at half of H3K27Ac-dense enhancers, so called super-enhancers, to control transcription of associated genes. We show that interaction of ETO2-GLIS2 with ETO2 complexes is an essential node for the transcriptional control by the fusion at enhancer elements. Indeed, ETO2-GLIS2 dimerizes and interacts with endogenous ETO2 via its NHR2 domains. An NHR2 peptide-interference strategy inhibits oligomerization, reverses the transcriptional activation at enhancers, promotes megakaryocytic differentiation and abrogates human AMKL cells maintenance in vivo. Finally, upregulation of ERG by ETO2-GLIS2 further strengthen enhancers formation as ERG is co-recruited generating a feed forward loop at these elements and its knockdown or genetic inactivation downregulates expression of ETO2-GLIS2 targets required for leukemic cells survival. We propose that the megakaryocytic differentiation arrest and self-renewal controlled by ETO2-GLIS2 results from an imbalance in the expression of master transcription factors imposed by aberrant chromatin structures at enhancers that may be disrupted by targeting the NHR2 interface. Disclosures No relevant conflicts of interest to declare.

An Approach to Definition of Genetic Alterations in Prostate Cancer

1992 ◽  
Vol 1 (1) ◽  
pp. 192-199 ◽  
Author(s):  
Sandra R. Wolman ◽  
Jill A. Macoska ◽  
Mark A. Micale ◽  
Wael A. Sakr
Keyword(s):  
Prostate Cancer ◽  
Genetic Alterations ◽  
Definition Of

scholarly journals Adrenocortical Carcinoma With Renal Vein Thrombus Extended to Inferior Vena Cava: A Case Report

2015 ◽  
Vol 100 (7-8) ◽  
pp. 1190-1193 ◽  
Author(s):  
Mohsen Ayati ◽  
Jafar Shahbazi ◽  
Ali Tehranchi ◽  
Elnaz Ayati ◽  
Yousef Rezaei
Keyword(s):  
Inferior Vena Cava ◽  
Adrenocortical Carcinoma ◽  
Renal Vein ◽  
Inferior Vena ◽  
Vena Cava ◽  
Venous Invasion ◽  
Survival Duration ◽  
Comprehensive Therapy ◽  
Advanced Stages ◽  
Rare Malignancy

Adrenocortical carcinoma (ACC) is a rare aggressive tumor. Renal vein and inferior vena cava (IVC) thrombi have been found as uncommon presentations of ACC; however, the implementation of comprehensive therapy has remained controversial in such cases. We report a case of a 46-year-old woman with a large ACC associated with the invasion of tumor to IVC confirmed by imaging and immunohistochemistry examinations. The patient was treated successfully using aggressive surgery, including adrenalectomy and thrombectomy adjunct to an adrenocorticolytic agent. However, she died of metastasis complications at 3-month follow-up period. ACC is a rare malignancy, mostly presenting in advanced stages with poor prognosis. Implementing aggressive surgical therapy might be effective for the management of such cases; however, the short survival duration in our case underscores the need for defining the precise therapy of metastatic ACC associated with venous invasion.

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