Gene Expression Profiling of Benign and Malignant Pheochromocytoma

Abstract

There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra-adrenal locations, and presence of germline mutations of genes pre-disposing to the tumor. Correcting for the confounding influence of nora-drenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less-differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype-phenotype relationships. Further progress on the basis of this database can be made from follow-up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers.

MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas

“…Transcriptomic studies representing targets of miRNA-based regulation are pivotal for the correct interpretation of miRNA findings. There have been six previous studies 11,[37][38][39][40][41] on gene expression profiling involving malignant pheochromocytomas to date. The studies of Dahia et al, 11 Björklund et al 37 and the most recent study of Waldmann et al 41 included only two, three and five malignant pheochromocytomas, respectively.…”

“…The studies of Dahia et al, 11 Björklund et al 37 and the most recent study of Waldmann et al 41 included only two, three and five malignant pheochromocytomas, respectively. Brouwers et al 38 examined 20 malignant tumors along with 70 sporadic and syndromic benign tumors: Gene Ontology Analysis of benign and malignant tumor comparison revealed the relevance of signal transduction changes. The significant gene sets established in two recent large-scale studies by Thouënnon et al 39 and Suh et al 40 are quite different, which indicates the need for further, large-scale gene expression profiling studies.…”

“…38,39 Among the downregulated mRNAs of Thouënnon's study, we have identified in silico predicted targets of miR-1225-3p overexpressed in recurring tumors eg ankyrin-1 (ANK1), protein kinase C-e (PRKCE), nuclear receptor interacting protein 2 (NRIP2).…”

Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: Antiproliferative effects of peptide analogues

“…Furthermore, our analysis of a huge PHEO microarray database with 70 benign and 20 malignant metastatic specimens has shown that up to 89% of genes were under-expressed in malignant primary tumors as compared to benign tumors (23). Interestingly, further detailed analysis of this database also revealed a differential expression of neuropeptide hormone receptors in subtypes of human PHEO.…”

Role of 18F-FDG PET/CT, 123I-MIBG SPECT, and CT in Restaging Patients Affected by Malignant Pheochromocytoma

“…The incidence in the general population is estimated to be less than 1 per 100,000 people per year [3]. The majority of PH are benign, while malignant tumors occur in about 10% of PH [4]. The most common metastatic sites for chromaffin cell tumors are local lymph nodes, bone, liver, and lung [5,6].…”