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Beta-catenin status effects in human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10)

ABSTRACT: We scored adrenocortical carcinomas and adenomas for abnormal beta-catenin staining, and sequenced the beta-catenin gene in some samples. We compared adrenocortincal carcinomas with and without abnormal beta-catenin staining and found many significant expression differences and significant results from enrichment testing. A similar comparison in the adenomas gave relatively few differences, and they did not correlate to differences found for the carcinomas. Abnormal beta-catenin staining was associated with mitotic rate and poorer patient survival in the carcinomas. In a second independent data set (given in a supplement) we again found beta-catenin associated with poor survival. The array data given is the same as GEO series GSE10927, with additional characteristics about beta-catenin, and new patient followup data. The analysis shown in a supplementary Excel file is also new. Human samples of 33 adrenocortical carcinomas, 22 adrenocortical adenomas, and 10 normal adrenal cortex samples, each from a different patient, had mRNA assays performed using Affymetrix HG_U133_plus_2 arrays, with 54675 probe-sets. 23 of the carcinomas were used in survival analysis. 27 additional samples without array data were also used in a survival analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Kuick Rork

PROVIDER: S-ECPF-GEOD-33371 | biostudies-other |

REPOSITORIES: biostudies-other

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Beta-catenin status effects in human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10)

Project description:We scored adrenocortical carcinomas and adenomas for abnormal beta-catenin staining, and sequenced the beta-catenin gene in some samples. We compared adrenocortincal carcinomas with and without abnormal beta-catenin staining and found many significant expression differences and significant results from enrichment testing. A similar comparison in the adenomas gave relatively few differences, and they did not correlate to differences found for the carcinomas. Abnormal beta-catenin staining was associated with mitotic rate and poorer patient survival in the carcinomas. In a second independent data set (given in a supplement) we again found beta-catenin associated with poor survival. The array data given is the same as GEO series GSE10927, with additional characteristics about beta-catenin, and new patient followup data. The analysis shown in a supplementary Excel file is also new.

2011-11-02 | GSE33371 | GEO

Beta-catenin status effects in human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10)

2011-11-02 | E-GEOD-33371 | biostudies-arrayexpress

Transcription profiling of human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10)

Project description:Human samples of 33 adrenocortical carcinomas, 22 adrenocortical adenomas, and 10 normal adrenal cortex samples, each from a different patient, had mRNA assays performed using Affymetrix HG_U133_plus_2 arrays, with 54675 probe-sets. Experiment Overall Design: Two supplementary files are attached below. The Adrenocortical_logs.xls file shows the log-transformed probe-set values and the results of a statistical analysis for each probe-set. The Readme file describes the columns of this log file.

2009-02-07 | E-GEOD-10927 | biostudies-arrayexpress

Human adrenocortical carcinomas (33), adenomas (22), and normal adrenal cortex (10), on Affymetrix HG_U133_plus_2 arrays

Project description:Human samples of 33 adrenocortical carcinomas, 22 adrenocortical adenomas, and 10 normal adrenal cortex samples, each from a different patient, had mRNA assays performed using Affymetrix HG_U133_plus_2 arrays, with 54675 probe-sets. We note that the same array data is in GEO series GSE33371, where we assayed the cancer samples for Beta-catenin staining or mutation, and make new comparisons based on those assays. Keywords: disease state analysis

2009-01-22 | GSE10927 | GEO

Long noncoding RNAs profiles of adrenocortical carcinomas, adrenocortical adenomas and normal adrenal cortex

Project description:Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours has been characterised by mRNA, microRNA and methylation expression signatures but it is unknown if this extends to lncRNAs. We sought to describe lncRNA expression signatures in adrenocortical carcinoma (ACC), adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC). RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using qRT-PCR.

2015-01-01 | GSE61359 | GEO

Transcription profiling by array of human adrenocortical carcinomas, adenomas and healthy adrenal cortex tissues

| S-ECPF-GEOD-10927 | biostudies-other

Human Cytochrome P450 2W1 Is Not Expressed in Adrenal Cortex and Is Only Rarely Expressed in Adrenocortical Carcinomas.

Project description:Human cytochome P450 2W1 (CYP2W1) enzyme is expressed in fetal colon and in colon tumors. The level of expression is higher in colon metastases than in the parent tumors and the enzyme is a possible drug target for treatment of colorectal cancer, as demonstrated in mouse xenograft studies. A previous study published in this journal reported that CYP2W1 is highly expressed in normal and transformed adrenal tissue. However, adrenal expression of CYP2W1 protein was not seen in previous studies in our research group. To clarify this inconsistency, we have used qRT-PCR and Western blotting with CYP2W1-specific antibodies to probe a panel of 27 adrenocortical carcinomas and 35 normal adrenal cortex samples. CYP2W1 mRNA expression is seen in all samples. However, significant CYP2W1 protein expression was found in only one tumor sample (a testosterone-producing adrenocortical carcinoma) and not in any normal tissue. Differences in the specificity of the CYP2W1 antibodies used in the two studies may explain the apparent discrepancy. We conclude that normal adrenal tissue lacks P450 2W1 enzyme expression; also, adrenocortical carcinomas generally do not express the enzyme. This information thus underline the colon cancer specificity of CYP2W1 enzyme expression and has implications for the development of anti-colon cancer therapies based on CYP2W1 as a drug target, since 2W1-dependent bioactivation of prodrugs for CYP2W1 will not take place in normal adrenal tissue or other non-transformed tissues.

| S-EPMC5012573 | biostudies-literature

Angiogenesis in the Normal Adrenal Fetal Cortex and Adrenocortical Tumors.

Project description:Angiogenesis plays an important role in several physiological and pathological processes. Pharmacological angiogenesis modulation has been robustly demonstrated to achieve clinical benefits in several cancers. Adrenocortical carcinomas (ACC) are rare tumors that often have a poor prognosis. In addition, therapeutic options for ACC are limited. Understanding the mechanisms that regulate adrenocortical angiogenesis along the embryonic development and in ACC could provide important clues on how these processes could be pharmacologically modulated for ACC treatment. In this report, we performed an integrative review on adrenal cortex angiogenesis regulation in physiological conditions and ACC. During embryonic development, adrenal angiogenesis is regulated by both VEGF and Ang-Tie signaling pathways. In ACC, early research efforts were focused on VEGF signaling and this pathway was identified as a good prognostic factor and thus a promising therapeutic target. However, every clinical trial so far conducted in ACC using VEGF pathway- targeting drugs, alone or in combination, yielded disappointing results. In contrast, although the Ang-Tie pathway has been pointed out as an important regulator of fetal adrenocortical angiogenesis, its role is yet to be explored in ACC. In the future, further research on the role and efficacy of modulating both Ang-Tie and VEGF pathways in ACC is needed.

| S-EPMC7957756 | biostudies-literature

Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas.

Project description:Somatic mutations in protein kinase A catalytic ? subunit (PRKACA) were found to be causative for 30-40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit II?. In this study, we linked for the first time the loss of RII? protein levels to the PRKACA mutation status and found the down-regulation of RII? to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.

| S-EPMC5427838 | biostudies-literature

Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers.

Project description:AimsTo determine clinicopathological criteria and molecular markers helpful in distinguishing adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs).Methods and resultsWe analysed retrospectively the clinical and pathological features of 50 adrenal cortical tumours, and tested the expression of miR483-3p by in-situ hybridization as well as the expression of IGF2 and Smad4 by immunohistochemistry. We found that tumour size, tumour weight, hormonal function and the Weiss system are all high-efficacy criteria for differentiating malignant from benign tumours (P < 0.001). MiR483-3p was overexpressed in 68% (17 of 25) of ACCs compared to 12% (three of 25) of ACAs (P < 0.05). Using a combination of miR483-3p and Smad4 improved diagnostic accuracy. Molecular markers were then tested in an independent set of 15 borderline tumours. We confirmed that the combined use of miR483-3p and Smad4 immunochemistry can complement the Weiss score in the diagnosis of ACC in cases that display borderline histology.ConclusionsTumour size, tumour weight, hormonal function and the Weiss system are useful clinicopathological criteria that can result in accurate diagnosis of most ACCs and ACAs. In challenging cases, miR483-3p and Smad4 expression may help in distinguishing these two entities.

| S-EPMC4282325 | biostudies-literature

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