The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors.
| Title: | The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors. |
|---|---|
| Authors: | Tacon LJ; Cancer Genetics Unit, Hormones and Cancer Group, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2006, Australia. ltacon@med.usyd.edu.au; Soon PS; Gill AJ; Chou AS; Clarkson A; Botling J; Stalberg PL; Skogseid BM; Robinson BG; Sidhu SB; Clifton-Bligh RJ |
| Source: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2009 Nov; Vol. 94 (11), pp. 4591-9. Date of Electronic Publication: 2009 Oct 09. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2017- : New York : Oxford University Press; Original Publication: Springfield, Ill. : Charles C. Thomas |
| MeSH Terms: | Gene Expression Regulation, Neoplastic*; Adrenal Cortex Neoplasms/*genetics ; Receptors, Glucocorticoid/*genetics; Adrenal Cortex Neoplasms/pathology ; DNA, Neoplasm/genetics ; DNA, Neoplasm/isolation & purification ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; RNA, Neoplasm/isolation & purification ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Reference Values ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation |
| Abstract: | 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. |
| Substance Nomenclature: | 0 (DNA, Neoplasm); 0 (NR3C1 protein, human); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 0 (Receptors, Glucocorticoid) |
| Entry Date(s): | Date Created: 20091013 Date Completed: 20100107 Latest Revision: 20091105 |
| Update Code: | 20260130 |
| DOI: | 10.1210/jc.2009-0546 |
| PMID: | 19820023 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't