Immunohistochemical Evidence of Dysregulation of the Mammalian Target of Rapamycin Pathway in Primary and Metastatic Pheochromocytomas

Ano de Publicação: 2012

AUTORIA

Alcides Chaux, Fadi Brimo, Nilda Gonzalez-Roibon, Smit Shah, Luciana Schultz,

Jean-Marc Rizk, Pedram Argani, Jessica Hicks, and George J. Netto

OBJECTIVE To characterize the status of the mammalian target of rapamycin pathway using formalin-fixed,

paraffin-embedded specimens from patients with primary and metastatic pheochromocytoma.

METHODS Tissue microarrays were built from 19 normal adrenal medullas, 39 primary pheochromocytomas,

and 8 unrelated metastatic pheochromocytomas. In 2 of the 8 cases of metastatic pheochromocytoma

tissues, samples from the primary tumor were available. The expression levels of

phosphatase and tensin homolog, phosphorylated Akt, phosphorylated S6, p27, and c-myc were

evaluated by immunohistochemistry.

RESULTS The levels of phosphatase and tensin homolog and p27 were greater in the nontumor tissue than

in the primary and metastatic pheochromocytomas. Increasing levels of phosphorylated Akt were

noted in the nontumor adrenal medulla, primary pheochromocytomas, and metastatic pheochromocytomas.

Finally, the levels of phosphorylated S6 were greater in the metastatic pheochromocytomas

than in the nontumor adrenal medulla and primary pheochromocytomas.

CONCLUSION We found evidence of dysregulation of the mammalian target of rapamycin pathway in primary

and metastatic pheochromocytomas, with increased phosphorylated S6 and phosphorylated Akt,

and decreased phosphatase and tensin homolog and p27 expression levels. Because the currently

available treatment modalities are less than optimal, our findings lend additional support to

continuing to explore the utility of mammalian target of rapamycin pathway-targeted therapy for