High Diagnostic and Prognostic Value of Steroidogenic Factor-1 Expression in Adrenal Tumors

Sbiera, Silviu; Schmull, Sebastian; Assié, Guillaume; Voelker, Hans-Ullrich; Kraus, Luitgard; Beyer, Melanie; Ragazzon, Bruno; Beuschlein, Felix; Willenberg, Holger S.; Hahner, Stefanie; Saeger, Wolfgang; Bertherat, Jérôme; Allolio, Bruno; Faßnacht, Martin

doi:10.1210/jc.2010-0653

Cited by 199 publications

(137 citation statements)

References 63 publications

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“…Overexpression of this enzyme involved in metastatic invasion is associated with reduced DFS and OS (Volante et al 2006); • staining for phospho-histone H3, a marker for mitotic cells, was shown to have a borderline correlation with OS in ACC, which was less significant than mitotic count (Duregon et al 2014a); • low expression of serum glucocorticoid kinase 1 (SGK1), an ubiquitous serine/threonine kinase regulated by growth factors, is correlated with shorter OS in ACC (Ronchi et al 2012); • Steroidogenic Factor-1 (SF-1) is a transcription factor, belonging to the nuclear receptor superfamily, that has an essential role in the development of adrenal glands and gonads (Lalli 2010). SF-1 expression is a hallmark of ACT and its higher expression levels in ACC are associated with reduced DFS and OS (Sbiera et al 2010, Duregon et al 2013b. In ACT cells, SF-1 regulates different sets of target genes according to its dosage (Doghman et al 2007a(Doghman et al , 2013.…”

Section: Immunohistochemical Markers Improve Prognostic Assessment Inmentioning

confidence: 99%

The next step: mechanisms driving adrenocortical carcinoma metastasis

Lalli

Luconi²

2018

Endocrine-Related Cancer

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Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization even when the primary tumor is diagnosed and surgically removed at an early stage. We highlight perspectives of future research in the domain and possible new therapeutic avenues based on targeting factors having an important role in the metastatic process of ACC.

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Section: Immunohistochemical Markers Improve Prognostic Assessment Inmentioning

confidence: 99%

The next step: mechanisms driving adrenocortical carcinoma metastasis

Lalli

Luconi²

2018

Endocrine-Related Cancer

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“…SF-1 induces proliferation of ACC cell lines and tumour growth in vivo (Doghman et al 2009) and its increased expression has been associated with a worse prognosis (Sbiera et al 2010). SF-1 inhibitors in ACC cell lines inhibited cell proliferation associated with SF-1 overexpression along with steroid hormone oversecretion and CYP21 and CYP17 mRNA expression (Doghman et al 2010).…”

Section: Molecular Profilementioning

confidence: 99%

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

Angelousi¹,

Dimitriadis²,

Zografos³

et al. 2017

Endocrine-Related Cancer

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Tumourigenesis is a relatively common event in endocrine tissues. Currently, specific guidelines have been developed for common malignant endocrine tumours, which also incorporate advances in molecular targeted therapies (MTT), as in thyroid cancer and in gastrointestinal neuroendocrine malignancies. However, there is little information regarding the role and efficacy of MTT in the relatively rare malignant endocrine tumours mainly involving the adrenal medulla, adrenal cortex, pituitary, and parathyroid glands. Due to the rarity of these tumours and the lack of prospective studies, current guidelines are mostly based on retrospective data derived from surgical, locoregional and ablative therapies, and studies with systemic chemotherapy. In addition, in many of these malignancies the prognosis remains poor with individual patients responding differently to currently available treatments, necessitating the development of new personalised therapeutic strategies. Recently, major advances in the molecular understanding of endocrine tumours based on genomic, epigenomic, and transcriptome analysis have emerged, resulting in new insights into their pathogenesis and molecular pathology. This in turn has led to the use of novel MTTs in increasing numbers of patients. In this review, we aim to present currently existing and evolving data using MTT in the treatment of adrenal, pituitary and malignant parathyroid tumours, and explore the current utility and effectiveness of such therapies and their future evolution.

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“…SF-1 also shows prognostic information: higher expression correlates with more advanced tumour stage, poorer clinical outcome, and shorter overall survival [68,69].…”

Section: Prace Poglądowementioning

confidence: 99%

“…The pipeline of diagnostic markers includes proliferation assessment by Ki-67 labelling index [181]. Similarly, steroidogenic factor-1 shows great diagnostic and prognostic value, as its increased expression correlates with more advanced tumour stage and poorer prognosis [68]. Other examples of molecular events that may be potentially used for this purpose include increased levels of insulin-like growth factor II, fibroblast growth factor receptors 1 and 4, or cyclins (D1, E1, and E2).…”

Section: Summary Final Conclusion and Future Opportunitiesmentioning

confidence: 99%

“…W większo-ści nowotworów wieku dziecięcego liczba kopii SF-1 jest zwiększona w wyniku posiadania dodatkowego chromosomu lub amplifikacji w 9q33 [65][66][67]. Receptor jądrowy steroidogennego czynnika 1 jest również przydatny jako marker rokowniczy: jego zwiększona ekspresja koreluje z bardziej zaawansowanym stadium nowotworu, gorszymi efektami leczenia i krótszym całkowitym czasem przeżycia [68,69].…”

Section: Prace Poglądoweunclassified

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Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

Szyszka

Grossman

Díaz‐Cano

et al. 2015

Endokrynologia Polska

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Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/-chemotherapy) are limited, and the results remain unsatisfactory. Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene. The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools. In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches. StreszczenieRak kory nadnercza charakteryzuje się niską wyleczalnością i wysokim ryzykiem nawrotu. Rokowanie jest złe, a 30-40% przypadków okazuje się być przerzutami już przy diagnozie. Obecnie dostępne opcje terapeutyczne (chirurgiczna resekcja z następującym adjuwantowym leczeniem mitotanem, czasem połączonym z chemoterapią) są ograniczone, a ich wyniki są mało satysfakcjonujące. Kluczowe zmiany molekularne przyczyniające się to rozwoju raka kory nadnercza to nadekspresja IGF2, mutacje inaktywujące TP53 oraz konstytutywna aktywacja szklaku sygnałowego Wnt/b-katenina poprzez mutacje aktywujące gen b-kateniny. Genetyczne przyczyny leżące u podstaw dziedzicznych zespołów nowotworowych dostarczyły wgląd w ich patogenezę molekularną. Zespoły: Li-Fraumeni, Beckwitha-Wiedemanna oraz Carneya, charakteryzujące się zwiększoną predyspozycją do nowotworów kory nadnercza, uwidoczniły określone geny podatności, odpowiednio: TP53, IGF2 oraz PRKAR1A. Dalsze badania potwierdziły udział tych genów także w nowotworach sporadycznych. Co istotne, badania transkryptomu wykazały istotne różnice między nowotworami złośli-wymi i łagodnymi, dostarczając potencjalnych opcji diagnostycznych. Podsumowując, wzbogacenie wiedzy na temat molekularnych podstaw, a szczególnie szlaków sygnałowych, które mogą być zaburzone w procesie nowotworzenia w obrębie kory nadnercza znacznie przyczyni się poprawieniu możliwości diagnostycznych, rokowniczych oraz leczniczych. (Endokrynol Pol 2016; 67 (4): 427-440) Słowa kluczowe: rak kory nadnerczy; nowotwory kory nadnercza; patologia molekularna; szlaki transdukcji sygnałów; zespoły n...

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High Diagnostic and Prognostic Value of Steroidogenic Factor-1 Expression in Adrenal Tumors

Abstract: SF-1 is a highly valuable immunohistochemical marker to determine the adrenocortical origin of an adrenal mass with high sensitivity and specificity. In addition, SF-1 expression is of stage-independent prognostic value in patients with ACC.

Cited by 199 publications

References 63 publications

The next step: mechanisms driving adrenocortical carcinoma metastasis

The next step: mechanisms driving adrenocortical carcinoma metastasis

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

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