The Akt pathway is one of the most common
molecular alterations in various human malignancies.
However, its involvement in nasopharyngeal carcinoma
(NPC) tumorigenesis has not been well established. In this
study, the status of Akt activation and expression of its
upstream and downstream molecules was investigated in 64
NPC and 38 non-malignant nasopharyngeal tissues by
immunohistochemistry. The hotspot mutations of PIK3CA,
encoding the p110α catalytic subunit of phosphatidylinositol
3-kinase (PI3K), were also determined in 25 of these NPC
tissues. No hotspot mutations were found in any of the
samples tested. Akt was activated in 27 (42.2%) and 23
(35.9%) NPCs, as indicated by p-Akt (Thr308) and p-Akt
(Ser473) immunoreactivity, respectively. PTEN loss did not
correlate statistically with activated Akt. However, a positive
correlation was observed between activated Akt and
phospho-epidermal growth factor receptor (p-EGFR),
suggesting that the EGFR signaling might be one of the
upstream regulators of the Akt pathway. The phosphorylation
of forkhead (FKHR) and Bcl-2 associated death domain
(BAD), but not mamalian target of rapamycin and glycogen
synthase kinase-3ß, was significantly correlated with Akt
activation. This implies that Akt promotes cell proliferation
(as estimated by Ki-67) and survival, at least, through the
inactivation of FKHR and BAD in NPC. Our data revealed
that the EGFR/PI3K/Akt signaling pathway is important in
NPC pathogenesis and that PIK3CA hotspot mutations are
rare in NPC.