Phospho‐m TOR  is not upregulated in metastatic   SDHB   paragangliomas | Zendy

Ghayee Hans K. | Zendy; Giubellino Alessio | Zendy; Click Arielle | Zendy; Kapur Payal | Zendy; Christie Alana | Zendy; Xie XianJin | Zendy; Martucci Victoria | Zendy; Shay Jerry W. | Zendy; Souza Rhonda F. | Zendy; Pacak Karel | Zendy

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Phospho‐m TOR is not upregulated in metastatic SDHB paragangliomas

Author(s) -

Ghayee Hans K.,

Giubellino Alessio,

Click Arielle,

Kapur Payal,

Christie Alana,

Xie XianJin,

Martucci Victoria,

Shay Jerry W.,

Souza Rhonda F.,

Pacak Karel

Publication year - 2013

Publication title -

european journal of clinical investigation

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.164

H-Index - 107

eISSN - 1365-2362

pISSN - 0014-2972

DOI - 10.1111/eci.12127

Subject(s) - sdhb , pi3k/akt/mtor pathway , immunohistochemistry , paraganglioma , cancer research , adrenal medulla , metastasis , downregulation and upregulation , medicine , pheochromocytoma , endocrinology , oncology , biology , cancer , pathology , signal transduction , catecholamine , gene , biochemistry , germline mutation , mutation

Background Pheochromocytomas ( PCC s)/paragangliomas ( PGL s) 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 / PGL s were analysed from two tertiary care centres. Immunohistochemistry ( IHC ) analysis was performed for phospho‐m TOR (pm TOR ), phospho‐ S 6K (p S 6K), phosphoinositide 3‐kinase ( P I3 K ), phospho‐4 EBP 1 (p4 EBP 1), HIF 1α and MIB ‐1 in 6 metastatic SDHB PCC / PGL s, 15 nonmetastatic PCC / PGL s, (including 1 TMEM 127 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 S 6K had significantly higher H scores in nonmetastatic PCC / PGL s than in metastatic SDHB PCC / PGL s. HIF 1α had significantly higher H scores in metastatic SDHB PCC / PGL s compared with nonmetastatic PCC / PGL s and normal adrenal medulla. No difference in H scores was seen with p4 EBP 1, P I3 K and MIB ‐1 when comparing metastatic SDHB PCC / PGL s and nonmetastatic PCC / PGL s. Significantly higher difference in pS 6K was seen in normal adrenal medullas compared to nonmetastatic PCC / PGL s and metastatic SDHB PCC / PGL s. Conclusion The present results suggest that the use of mTOR inhibitors alone for metastatic SDHB PCC / PGL s may not achieve good therapeutic efficacy in patients.

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