Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2

Huynh, Thanh‐Truc; Pacák, Karel; Brouwers, Frederieke M.; Abu‐Asab, Mones; Worrell, Robert A.; Walther, M; Elkahloun, Abdel G.; Goldstein, David S.; Cleary, Susannah; Eisenhofer, Graeme

doi:10.1530/eje.1.01987

Cited by 49 publications

(47 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Saveanu et al (37) observed a lower NET messenger RNA expression in VHL-related PPGLs than sporadic PPGLs, whereas expression of NET in RET-related PPGLs was higher. We observed a cytoplasmic staining for NET and VMAT-1 as previously reported by Huyhn et al (36). Our study confirms genotype-dependent differences in the expression of NET and VMAT-1.…”

Section: Discussionsupporting

confidence: 92%

“…Differences in the expression of catecholamine transporters have been reported between RET-and VHL-related tumors (36,37). Huyhn et al (36) showed that RET-related PPGLs expressed more NET messenger RNA and protein than VHL-related tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Huyhn et al (36) showed that RET-related PPGLs expressed more NET messenger RNA and protein than VHL-related tumors. In contrast, a higher expression of VMAT-1 was found in VHL-related tumors, although this was not confirmed at the protein level.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

et al. 2015

View full text Add to dashboard Cite

123 I-metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy plays an important role in the diagnostic evaluation of patients with pheochromocytoma and paraganglioma (PPGL). 123 I-MIBG targets cell membrane and vesicular catecholamine transporters of chromaffin cells and facilitates localization of the primary tumor and metastatic lesions. Its specificity for the diagnosis of adrenomedullary chromaffin cell tumors can be jeopardized by physiologic uptake by the normal adrenal medulla. The aim of this study was to distinguish between PPGLs and normal adrenal glands by evaluating semiquantitative 123 I-MIBG uptake and to examine genotype-specific differences in correlation with expression of catecholamine transporter systems. Methods: Sixty-two PPGLs collected from 57 patients with hereditary mutations in SDHA (n 5 1), SDHB (n 5 2), and SDHD (n 5 4) (SDH is succinate dehydrogenase); von Hippel-Lindau (VHL; n 5 2); RET (n 5 12); neurofibromin 1 (NF1; n 5 2); and MYC-associated factor X (MAX; n 5 1), and with sporadic PPGLs (n 5 33) were investigated. Preoperative planar and SPECT images were semiquantitatively analyzed using uptake measurements. Tumor-to-liver and normal adrenal-to-liver ratios were calculated and correlated with clinical characteristics including genotype, tumor size, and plasma metanephrines concentrations. The expression of norepinephrine transporter (NET) and vesicular monoamine transporter (VMAT-1) was evaluated immunohistochemically in paraffin-embedded tumor tissues. Results: Mean tumor-to-liver ratios of PPGL lesions were significantly higher than normal adrenal-to-liver ratios (P , 0.001). Cutoff values to distinguish between physiologic and pathologic adrenal uptake were established at 0.7 (100% sensitivity, 10.3% specificity) and 4.3 (100% specificity, 66.1% sensitivity). No statistically significant differences in 123 I-MIBG uptake were found across PPGLs of different genotypes. Mean NET expression in hereditary cluster 2 (RET, NF1, MAX) and apparently sporadic tumors was significantly higher than for hereditary cluster 1 (SDHx, VHL) PPGLs (P 5 0.011 and 0.006, respectively). Mean VMAT-1 expression in hereditary cluster 1 PPGLs was significantly higher than for cluster 2 tumors (P 5 0.010). 123 I-MIBG uptake significantly correlated with maximum tumor diameter (P 5 0.002). 123 I-MIBG uptake, however, did not correlate with either NET or VMAT-1 expression. Conclusion: Liver-normalized semiquantitative 123 I-MIBG uptake may be helpful to distinguish between pheochromocytoma and physiologic adrenal uptake. Genotype-specific differences in the expression of NET and VMAT-1 do not translate into differences in 123 I-MIBG uptake.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

et al. 2015

View full text Add to dashboard Cite

show abstract

“…RNA was extracted from frozen phaeochromocytoma tumour samples and reverse transcribed as previously described (Huynh et al 2005). Quantitative PCR was performed with an ABI 7000 Sequence Detector (Applied Biosystems, Foster City, CA, USA) using PCR conditions consisting of 40 cycles of 15 s at 95 8C and 1 min at 60 8C.…”

Section: Quantitative Pcrmentioning

confidence: 99%

Neuropeptide Y expression in phaeochromocytomas: relative absence in tumours from patients with von Hippel–Lindau syndrome

Cleary¹,

Phillips²,

Huynh³

et al. 2007

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Phaeochromocytomas are rare neuroendocrine tumours that produce catecholamines and numerous secretory proteins and peptides, including neuropeptide Y (NPY), a vasoactive peptide with influences on blood pressure. The production of catecholamines and NPY by phaeochromocytomas is highly variable. This study examined influences of hereditary factors and differences in catecholamine production on tumour expression of NPY, as assessed by quantitative PCR, enzyme immunoassay and immunohistochemistry. Phaeochromocytomas included hereditary adrenaline-producing tumours (adrenergic phenotype) in multiple endocrine neoplasia type 2 (MEN 2), predominantly noradrenaline-producing tumours (noradrenergic phenotype) in von Hippel-Lindau (VHL) syndrome, and other adrenergic and noradrenergic tumours where there was no clear hereditary syndrome. NPY levels in phaeochromocytomas from VHL patients were lower (P!0 . 0001) than in those from MEN 2 patients for both mRNA (84-fold difference) and the peptide (99-fold difference). These findings were supported by immunohistochemistry. NPY levels were also lower in VHL tumours than in those where there was no hereditary syndrome. Relative absence of expression of NPY in phaeochromocytomas from VHL patients when compared with other groups appears to be largely independent of differences in catecholamine production and is consistent with a unique phenotype in VHL syndrome.

show abstract

“…Another important catecholeamine transporter in noradrenaline-producing chromaffin cells or neurons is SLC18A1 (also called VMAT1; vesicular monoamine transporter 1). The differential expression levels of its transcript have been discussed in previous studies concerning neuroblastoma (33), phaeochromocytoma (34,35), as well as in gastrointestinal endocrine tumors (36). In a recent study, Revet and colleagues showed a connection of the Phox2-pathway to the Delta-Notch pathway via the homeobox transcription factor MSX1 (37).…”

Section: Discussionmentioning

confidence: 99%

The Phox2 pathway is differentially expressed in neuroblastoma tumors, but no mutations were found in the candidate tumor suppressor gene PHOX2A

Wilzén

Nilsson²,

Sjöberg³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common solid tumor in childhood. By microarray expression analysis (Affymetrix HU133A) important players in the noradrenalin biosynthesis pathway (DBH, DDC, GATA2, GATA3, PHOX2A, PHOX2B, SLC6A2 SLC18A1 and TH) were found to be among the top ranked genes in showing lower expression in unfavorable NB tumor types as compared to favorable ones. By quantitative PCR with TaqMan, this result was significantly verified for all transcripts (p<0.05, one-tailed) in a new set of 11 primary NB tumors (5 favorable vs. 6 unfavorable). PHOX2A, a downstream target of Phox2b, was found to be the sixth ranked gene from the microarray gene list. Since the PHOX2A gene is localized in a tumor suppressor candidate region at 11q, we screened this gene for mutations by DNA sequencing in 47 tumors of different stages. However, no critical changes were found that could support its role in tumor development or progression. Overall, the findings in this study either suggest that expression of this pathway could be a predictive differentiation marker of NB tumors, or our results could also imply that the noradrenalin biosynthesis pathway is involved in tumor pathogenesis.

show abstract

Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2

Abstract: The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines.

Cited by 49 publications

References 27 publications

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

Neuropeptide Y expression in phaeochromocytomas: relative absence in tumours from patients with von Hippel–Lindau syndrome

The Phox2 pathway is differentially expressed in neuroblastoma tumors, but no mutations were found in the candidate tumor suppressor gene PHOX2A

Contact Info

Product

Resources

About

Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2

Abstract: The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines.

Cited by 49 publications

References 27 publications

Semiquantitative 123I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

Semiquantitative 123I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

Neuropeptide Y expression in phaeochromocytomas: relative absence in tumours from patients with von Hippel–Lindau syndrome

The Phox2 pathway is differentially expressed in neuroblastoma tumors, but no mutations were found in the candidate tumor suppressor gene PHOX2A

Contact Info

Product

Resources

About

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters