Phospho-mTOR is not upregulated in metastatic SDHB paragangliomas

Hans K Ghayee; Alessio Giubellino; Arielle Click; Payal Kapur; Alana Christie; Xian-Jin Xie; Victoria Martucci; Jerry W Shay; Rhonda F Souza; Karel Pacak

doi:10.1111/eci.12127

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Phospho-mTOR is not upregulated in metastatic SDHB paragangliomas

Journal article

Open access

Peer reviewed

Phospho-mTOR is not upregulated in metastatic SDHB paragangliomas

Hans K Ghayee, Alessio Giubellino, Arielle Click, Payal Kapur, Alana Christie, Xian-Jin Xie, Victoria Martucci, Jerry W Shay, Rhonda F Souza and Karel Pacak

European journal of clinical investigation, Vol.43(9), pp.970-977

09/2013

DOI: 10.1111/eci.12127

PMCID: PMC4716658

PMID: 23889685

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Abstract

Pheochromocytomas (PCCs)/paragangliomas (PGLs) are neuroendocrine tumours that may cause arrhythmia and death if untreated. Treatment for patients with metastatic tumours is lacking. As new PCC/PGL susceptibility genes are discovered that are associated with the mTOR pathway, treatment targets focusing on this pathway are being intensively explored. Twenty-one human PCC/PGLs were analysed from two tertiary care centres. Immunohistochemistry (IHC) analysis was performed for phospho-mTOR (pmTOR), phospho-S6K (pS6K), phosphoinositide 3-kinase (PI3K), phospho-4EBP1 (p4EBP1), HIF1α and MIB-1 in 6 metastatic SDHB PCC/PGLs, 15 nonmetastatic PCC/PGLs, (including 1 TMEM127 PCC and 1 nonmetastatic SDHB PGL) and 6 normal adrenal medullas. The product of the intensity of stain and percentage of cells stained was calculated as an H score. Using a two-sample t-test and paired t-test, pmTOR and pS6K had significantly higher H scores in nonmetastatic PCC/PGLs than in metastatic SDHB PCC/PGLs. HIF1α had significantly higher H scores in metastatic SDHB PCC/PGLs compared with nonmetastatic PCC/PGLs and normal adrenal medulla. No difference in H scores was seen with p4EBP1, PI3K and MIB-1 when comparing metastatic SDHB PCC/PGLs and nonmetastatic PCC/PGLs. Significantly higher difference in pS6K was seen in normal adrenal medullas compared to nonmetastatic PCC/PGLs and metastatic SDHB PCC/PGLs. The present results suggest that the use of mTOR inhibitors alone for metastatic SDHB PCC/PGLs may not achieve good therapeutic efficacy in patients.

Adrenal Medulla - metabolism

Up-Regulation

MAP Kinase Signaling System - physiology

Ribosomal Protein S6 Kinases - metabolism

TOR Serine-Threonine Kinases - metabolism

Paraganglioma - genetics

Humans

Ubiquitin-Protein Ligases - metabolism

Paraganglioma - drug therapy

Male

Phosphatidylinositol 3-Kinases - metabolism

Mutation - genetics

Phosphoproteins - metabolism

TOR Serine-Threonine Kinases - antagonists & inhibitors

Neoplasm Metastasis

Succinate Dehydrogenase - genetics

Hypoxia-Inducible Factor 1, alpha Subunit - metabolism

Paraganglioma - metabolism

Female

Adaptor Proteins, Signal Transducing - metabolism

RNA-Binding Proteins - metabolism

Details

Title: Subtitle: Phospho-mTOR is not upregulated in metastatic SDHB paragangliomas
Creators: Hans K Ghayee - Department of Internal Medicine, VA North Texas Health Care System, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
Alessio Giubellino
Arielle Click
Payal Kapur
Alana Christie
Xian-Jin Xie
Victoria Martucci
Jerry W Shay
Rhonda F Souza
Karel Pacak
Resource Type: Journal article
Publication Details: European journal of clinical investigation, Vol.43(9), pp.970-977
DOI: 10.1111/eci.12127
PMID: 23889685
PMCID: PMC4716658
NLM abbreviation: Eur J Clin Invest
ISSN: 0014-2972
eISSN: 1365-2362
Publisher: England
Grant note: Z01 HD008735-08 / Intramural NIH HHS C06 RR030414 / NCRR NIH HHS
Language: English
Date published: 09/2013
Academic Unit: Preventive and Community Dentistry; Biostatistics; Dental Research
Record Identifier: 9983917683102771

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