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- Title
Phospho-m TOR is not upregulated in metastatic SDHB paragangliomas.
- Authors
Ghayee, Hans K.; Giubellino, Alessio; Click, Arielle; Kapur, Payal; Christie, Alana; Xie, Xian‐Jin; Martucci, Victoria; Shay, Jerry W.; Souza, Rhonda F.; Pacak, Karel
- Abstract
Background 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 m TOR pathway, treatment targets focusing on this pathway are being intensively explored. Design Twenty-one human PCC/ PGLs were analysed from two tertiary care centres. Immunohistochemistry ( IHC) analysis was performed for phospho-m TOR (pm TOR), phospho- S6K (p S6K), phosphoinositide 3-kinase ( PI3 K), phospho-4 EBP1 (p4 EBP1), 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. Results Using a two-sample t-test and paired t-test, pm TOR and p S6K 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 p4 EBP1, PI3 K 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. Conclusion The present results suggest that the use of mTOR inhibitors alone for metastatic SDHB PCC/ PGLs may not achieve good therapeutic efficacy in patients.
- Subjects
RAPAMYCIN; PHOSPHORYLATION; PARAGANGLIOMA; PHEOCHROMOCYTOMA; NEUROENDOCRINE tumors; ARRHYTHMIA
- Publication
European Journal of Clinical Investigation, 2013, Vol 43, Issue 9, p970
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/eci.12127