Diagnostic and prognostic role of SF1, IGF2, Ki67, p53, adiponectin, and leptin receptors in human adrenal cortical tumors

Babińska, Anna; Pęksa, Rafał; Wiśniewski, Piotr; Świątkowska−Stodulska, Renata; Sworczak, Krzysztof

doi:10.1002/jso.24665

Cited by 16 publications

(13 citation statements)

References 24 publications

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“…The discovery of an adrenal tumor in imaging studies requires an assessment of its hormonal activity and of the risk of primary neoplasm as well as metastatic lesions of the adrenal gland [4,5,34,37,39].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies indicate that adrenal tumors in patients without clinical features of hormonal disorders may exhibit subclinical adrenal hormone secretion [10,19,39,40]. Many researchers showed that incidentally dis- covered adrenal tumors are associated with increased risk of cardiovascular diseases even in cases without any clinical signs of hormonal oversecretion [22,24,41].…”

Section: Discussionmentioning

confidence: 99%

“…Many researchers showed that incidentally dis- covered adrenal tumors are associated with increased risk of cardiovascular diseases even in cases without any clinical signs of hormonal oversecretion [22,24,41]. In particular, this concerns patients with subclinical glucocorticoid and mineralocorticoid excess due to adrenal cortex tumors, and catecholamines due to adrenal medulla tumors [20,39,42,43]. Nevertheless, there are no universally accepted hormonal criteria for SCS exclusion.…”

Section: Discussionmentioning

confidence: 99%

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Adipokine and cytokine levels in non-functioning adrenal incidentalomas (NFAI)

2018

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Due to the fact that overweight or obesity is accompanied by hormonally active adrenal tumors: Cushing Syndrome-(CS) and Subclinical Cushing Syndrome (SCS), it is of high interest the correlation between different adipokines and cytokines secreted by adipose tissue, with metabolic disorders and hormonal activity in this group. Even in non-functioning adrenal incidentalomas (NFAI) elevated risk for cardiovascular disease and metabolic syndrome was demonstrated. The aim of the study was to investigate plasma adiponectin, leptin, resistin, tumor necrosis factor α (TNFα), interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1) levels in patients with NFAIs and healthy subjects. The study included 18 NFAI patients and 18 healthy subjects. The groups were homogeneous in terms of age, sex and body mass index (BMI). Patients with NFAI showed significantly higher circulating levels of pro-inflammatory cytokines compared to healthy controls (MCP 1: p < 0.001; TNFα p = 0.021; IL6 p = 0.012). On the other hand, adiponectin concentration was significantly lower in the NFAI group (p = 0.034). The serum leptin and resistin concentrations did not differ significantly between the two groups. Acquired results were not dependent on glucocorticoid and catecholamine secretion in NFAI patients. Also, there were no clear correlations between BMI and cytokine levels. It is possible that increased risk for cardiovascular and metabolic diseases reported in NFAI patients is at least partially dependent on adipose tissue activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Adipokine and cytokine levels in non-functioning adrenal incidentalomas (NFAI)

2018

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“…In fact, it was shown in vitro that IGF2 induces proliferation, but its overexpression does not modify the phenotypic and molecular features of ACC cells 140 . In contrast, a study that assessed IGF2 protein expression and overall survival (OS) found that high IGF2 expression is associated with longer OS, suggesting that IGF2 is not a prognostic factor for ACC progression or metastasis 141 . Only in adult ACTs were differences in IGF2 expression observed between ACA and ACC, while in pediatric ACTs, the IGF1R gene was overexpressed in carcinomas 142 .…”

Section: Adult Adrenocortical Carcinomasmentioning

confidence: 96%

The human adrenal cortex: growth control and disorders

Lotfi¹,

Kremer²,

Passaia³

et al. 2018

Clinics

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This review summarizes key knowledge regarding the development, growth, and growth disorders of the adrenal cortex from a molecular perspective. The adrenal gland consists of two distinct regions: the cortex and the medulla. During embryological development and transition to the adult adrenal gland, the adrenal cortex acquires three different structural and functional zones. Significant progress has been made in understanding the signaling and molecules involved during adrenal cortex zonation. Equally significant is the knowledge obtained regarding the action of peptide factors involved in the maintenance of zonation of the adrenal cortex, such as peptides derived from proopiomelanocortin processing, adrenocorticotropin and N-terminal proopiomelanocortin. Findings regarding the development, maintenance and growth of the adrenal cortex and the molecular factors involved has improved the scientific understanding of disorders that affect adrenal cortex growth. Hypoplasia, hyperplasia and adrenocortical tumors, including adult and pediatric adrenocortical adenomas and carcinomas, are described together with findings regarding molecular and pathway alterations. Comprehensive genomic analyses of adrenocortical tumors have shown gene expression profiles associated with malignancy as well as methylation alterations and the involvement of miRNAs. These findings provide a new perspective on the diagnosis, therapeutic possibilities and prognosis of adrenocortical disorders.

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“…73 only one study reported that high immunostaining of igF2 correlated with longer oS in a small group of patients (N.=20). 76 Moreover, since its high prevalence in acc, igF2 overexpression could not be useful for the classification of ACC derived by transcriptome analyses. 12 different studies demonstrated no differences in igF1 mrNa level between acc and aca or normal adrenal gland.…”

Section: The Igf System In Adult Adrenocortical Carcinomamentioning

confidence: 99%

The role of insulin-like growth factor system in the adrenocortical tumors

Altieri¹,

Colao²,

Faggiano³

2018

Minerva Endocrinol

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The different presentation of adrenocortical tumors in benign adenoma (aca) or adrenocortical carcinoma (acc) is related to the variability at the molecular level. The insulin-like growth factor (igF) system is one of the most frequently altered pathways in acc. in this review we will critically analyze the evidence regarding the pathogenic role of the igF system in adrenal tumorigenesis, focusing on acc. We will also examine the preclinical and clinical studies which investigated the targeting of the igF system as a therapeutic approach in acc. EVIDENCE ACQUISITION: The IGF system plays a crucial role in the embryogenesis of adrenal glands. No significant alterations of the igF system were observed in aca. in acc, the IGF2 overexpression is one of the most frequent molecular change presented in more than 85% of cases. However, IGF2 seems to be only a tumor progression factor which requires additional hits to trigger adrenal tumorigenesis. also, the igF1 receptor (igF1r) appears to be higher expressed in acc. Many igF1r target-drugs have been developed to inhibit the activation of the igF system. eVideNce SYNTHeSiS: Preclinical studies using antibody or tyrosine kinase which target the igF1r, or the dualtargeting of igF1r and insulin receptor (ir) reduced acc cells proliferation both in vitro and in vivo in mouse xenograft model. However, these promising results were not confirmed in clinical trials. coNclUSioNS: Nowadays, predictive markers for the response of target-igF therapy are missing and further studies which investigate new molecular markers and evaluate the entire igF receptors, including the ir, are urgently needed.

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Diagnostic and prognostic role of SF1, IGF2, Ki67, p53, adiponectin, and leptin receptors in human adrenal cortical tumors

Abstract: The presented data indicate that immunohistochemical assessment (of IGF2, SF1, Adipo R1, and R2 receptors' expression) may be useful in making the diagnosis of uncertain ACC cases.

Cited by 16 publications

References 24 publications

Adipokine and cytokine levels in non-functioning adrenal incidentalomas (NFAI)

Adipokine and cytokine levels in non-functioning adrenal incidentalomas (NFAI)

The human adrenal cortex: growth control and disorders

The role of insulin-like growth factor system in the adrenocortical tumors

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