AKT and PTEN expression in human gastrointestinal carcinoid tumors.

Activation of Akt (protein kinase B) and loss of phosphatase and tensin homolog (PTEN) expression have been associated with disease recurrence and reduced survival in several cancers. We evaluated the expression patterns and prognostic value of active, phosphorylated Akt (pAkt) and PTEN in gastrointestinal (GI) carcinoid tumors. Total Akt, pAkt, and PTEN expression was assessed by Western blot analysis in 14 tumor samples from patients with GI carcinoid tumors. Expression levels were quantified with volume analysis software and correlated with clinical parameters. Total Akt, pAkt, and PTEN proteins were detectable in all tumor samples. The expression of activated pAkt and pAkt:PTEN ratios were significantly associated with elevated serum chromogranin A measurements (r=0.77 and 0.78, respectively, P</=0.02 for both). In addition, pAkt:PTEN expression ratios positively correlated with older age (r=0.65, P=0.017). Increased pAkt and pAkt:PTEN expression both were associated with reduced survival (r= -0.51, P=0.06 and r= -0.50, P=0.09, respectively). Patients with pAkt:PTEN ratios greater than one also had dramatically reduced overall survival, but this finding did not achieve statistical significance (36 vs. 153 months, P=0.19). These data suggest that pAkt and PTEN expression levels may be useful tools in understanding tumor biology and perhaps predicting survival in patients with carcinoid tumors. Furthermore, cumulative mutations may lead to upregulation of pAkt and loss of PTEN expression as patients age explaining why older age is associated with a worse prognosis in patients with carcinoid tumors.