Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

Krijger, Ronald R. de; Papathomas, Thomas

doi:10.1007/s00428-011-1166-y

Cited by 54 publications

(49 citation statements)

References 82 publications

(145 reference statements)

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“…The current pathological scoring system (Weiss score) is limited by a lack of reproducibility and lacks diagnostic accuracy in so-called 'borderline malignant' tumours with a Weiss score of 2 or 3 (Lau & Weiss 2009, de Krijger & Papathomas 2012. The assessment of malignant potential in adrenocortical tumour variants and/or paediatric adrenocortical neoplasms can be challenging and requires an experienced histopathologist; accordingly, applying the Weiss scoring system could tilt the diagnosis toward malignancy in oncocytic tumours and/or tumours in the paediatric setting (Dehner & Hill 2009, Papotti et al 2014, whereas underdiagnosis could possibly be the case when confronted with myxoid variants (Lau & Weiss 2009, de Krijger & Papathomas 2012, Papotti et al 2014. A biomarker that determines malignancy in adrenal tumours would be an important improvement in diagnostic certainty that can underpin therapeutic strategies such as adjuvant mitotane treatment and intensity and duration of follow-up (Young 2007).…”

Section: :9mentioning

confidence: 99%

Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas

Creemers

Koetsveld

Kemenade

et al. 2016

Endocrine-Related Cancer

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Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Discrimination of ACCs from adrenocortical adenomas (ACAs) is challenging on both imaging and histopathological grounds. High IGF2 expression is associated with malignancy, but shows large variability. In this study, we investigate whether specific methylation patterns of IGF2 regulatory regions could serve as a valuable biomarker in distinguishing ACCs from ACAs. Pyrosequencing was used to analyse methylation percentages in DMR0, DMR2, imprinting control region (ICR) (consisting of CTCF3 and CTCF6) and the H19 promoter. Expression of IGF2 and H19 mRNA was assessed by realtime quantitative PCR. Analyses were performed in 24 ACCs, 14 ACAs and 11 normal adrenals. Using receiver operating characteristic (ROC) analysis, we evaluated which regions showed the best predictive value for diagnosis of ACC and determined the diagnostic accuracy of these regions. In ACCs, the DMR0, CTCF3, CTCF6 and the H19 promoter were positively correlated with IGF2 mRNA expression (P < 0.05). Methylation in the most discriminating regions distinguished ACCs from ACAs with a sensitivity of 96%, specificity of 100% and an area under the curve (AUC) of 0.997 ± 0.005. Our findings were validated in an independent cohort of 9 ACCs and 13 ACAs, resulting in a sensitivity of 89% and a specificity of 92%. Thus, methylation patterns of IGF2 regulatory regions can discriminate ACCs from ACAs with high diagnostic accuracy. This proposed test may become the first objective diagnostic tool to assess malignancy in adrenal tumours and facilitate the choice of therapeutic strategies in this group of patients.

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Section: :9mentioning

confidence: 99%

Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas

Creemers

Koetsveld

Kemenade

et al. 2016

Endocrine-Related Cancer

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“…A study aiming to validate especially the first part of the algorithm, the presence of reticulin fibre disruptive changes, in 178 adrenocortical tumors, showed that a specific training increased the interobserver reproducibility to 86% (Duregon et al 2013a). Specifically for cortical tumor variants like oncocytic and myxoid subtypes this algorithm might be I 1 0 0 II 2 0 0 III 1, 2 1 0 3, 4 0, 1 0 IV 1-4 0, 1 1 applicable (Table 2; Papotti et al 2010, Duregon et al 2011, de Krijger & Papathomas 2012.…”

Section: Current Tools To Diagnose Accsmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

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Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

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“…Malignant adrenal tumors, which include neuroblastoma, adrenocortical carcinoma [11] with its oncocytic variant [12] and a minority of adrenal pheochromocytomas, are extremely rare, with an incidence of 1-2 per million population annually.…”

Section: Incidencementioning

confidence: 99%

Adrenal Oncocytic Neoplasm: A Systematic Review

Mearini¹,

Sordo

Costantini³

et al. 2012

Urol Int

102

164

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Introduction: Oncocytic neoplasms as tumors arising in the adrenal glands are rare, usually considered as nonfunctional and benign. In the current literature, there are extremely limited reports of adrenal oncocytic neoplasms; as to date, only 147 cases have been described. The rarity of the event prompted this study which reviews and presents the incidence, histology, diagnosis and therapy of adrenal oncocytic neoplasms. Materials and Methods: A review by systematic literature search was done using the MEDLINE®/Cochrane libraries from 1950 to date using the medical subject headings ‘oncocytoma', ‘adrenal gland', ‘adrenal oncocytoma', ‘adrenal oncocytic neoplasm' and ‘adrenal oncocytic carcinoma'. Results: Adrenal oncocytic neoplasm is a rare disease, usually incidentally detected because only 17% are functional adrenal masses. The typical oncocyte displays abundant granular eosinophilic cytoplasm, due to the accumulation of mitochondria. Computed tomography and magnetic resonance imaging are not able to identify or differentiate benign and malignant oncocytic neoplasms. The mainstay of therapy is adrenalectomy, recently performed by laparoscopy. The prognosis is good for benign tumors, while adrenocortical oncocytic carcinoma has a poor survival rate of only 5 years. Conclusions: Adrenal oncocytic neoplasm, a rare and mostly benign tumor, usually presents as an incidental, large adrenal mass; surgery is the mainstay of therapy, by means of laparoscopy which is now the most diffuse approach to adrenalectomy.

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Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

Cited by 54 publications

References 82 publications

Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas

Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Adrenal Oncocytic Neoplasm: A Systematic Review

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