• Eur. J. Clin. Invest. · Sep 2013

    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.
    • Department of Internal Medicine, VA North Texas Health Care System, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
    • Eur. J. Clin. Invest. 2013 Sep 1; 43 (9): 970977970-7.

    BackgroundPheochromocytomas (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.DesignTwenty-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.ResultsUsing 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.ConclusionThe present results suggest that the use of mTOR inhibitors alone for metastatic SDHB PCC/PGLs may not achieve good therapeutic efficacy in patients.Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

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