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The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors
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2009 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 11, 4591-4599 p.Article in journal (Refereed) Published
Abstract [en]

CONTEXT:

Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. The Weiss score is the most widely accepted method for distinguishing an ACC from an adrenocortical adenoma (ACA); however, in borderline cases, accurate diagnosis remains problematic. We recently discovered that the glucocorticoid receptor (GR) gene NR3C1 is significantly up-regulated in ACCs compared with ACAs in global gene expression studies.

OBJECTIVE:

Our objective was to study GR expression in adrenocortical tumors (ACTs) and to assess its utility as an adjunct to the Weiss score.

DESIGN:

Microarray analysis, real-time quantitative RT-PCR (qPCR), immunohistochemistry, Western blot, and direct sequencing were performed.

RESULTS:

Analysis of 28 ACTs by microarray and 49 ACTs by qPCR found NR3C1 expression to be up-regulated in ACCs compared with ACAs (P < 0.001). Western blotting and RT-PCR confirmed the presence of the GRalpha isoform in ACCs, and no mutations were detected on direct sequencing. Immunohistochemistry for GR in an overlapping cohort of ACTs demonstrated strongly positive nuclear staining in 31 of 33 ACCs (94%), with negative staining in 40 of 41 ACAs (98%) (P < 0.001). This finding was validated in an external cohort of ACTs, such that 14 of 18 ACCs (78%) demonstrated positive nuclear staining whereas 32 of 33 ACAs (94%) were negative (P < 0.001).

CONCLUSIONS:

The immunohistochemical finding of nuclear GR staining identified ACCs with high diagnostic accuracy. We propose that GR immunohistochemistry may complement the Weiss score in the diagnosis of ACC in cases that display borderline histology. The possibility that GR is transcriptionally active in these tumors, and may therefore be a therapeutic target, requires further study.

Place, publisher, year, edition, pages
2009. Vol. 94, no 11, 4591-4599 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-110611DOI: 10.1210/jc.2009-0546ISI: 000271470800060PubMedID: 19820023OAI: oai:DiVA.org:uu-110611DiVA: diva2:277449
Available from: 2009-11-18 Created: 2009-11-18 Last updated: 2017-12-12Bibliographically approved

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Botling, JohanStålberg, Peter L. H.Skogseid, Britt M.

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Department of Genetics and PathologyEndocrine SurgeryDepartment of Medical Sciences
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Journal of Clinical Endocrinology and Metabolism
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