Am J Translational Res 1(2):291-299,2009
Original Article
AKT and PTEN expression in human gastrointestinal carcinoid tumors
Susan C. Pitt, Ruth Davis, Muthusamy Kunnimalaiyaan, Herbert Chen
Department of Surgery, University of Wisconsin, H4/750 Clinical Science Center, 600 Highland Avenue, Madison,
WI 53792
Received January 26, 2009; accepted January, 2009; available online January, 2009
Abstract: 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. (AJTR901002).
Key words: Carcinoid tumors, Akt, PTEN, chromogranin A, survival
Full Text PDF
Address all correspondence to:
Herbert Chen, M.D., FACS
600 Highland Avenue
H4/750 Clinical Science Center
Madison, WI 53792-3284
Phone: 608-263-1387
Fax: 608-263-7652
Email: chen@surgery.wisc.edu
Original Article
AKT and PTEN expression in human gastrointestinal carcinoid tumors
Susan C. Pitt, Ruth Davis, Muthusamy Kunnimalaiyaan, Herbert Chen
Department of Surgery, University of Wisconsin, H4/750 Clinical Science Center, 600 Highland Avenue, Madison,
WI 53792
Received January 26, 2009; accepted January, 2009; available online January, 2009
Abstract: 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. (AJTR901002).
Key words: Carcinoid tumors, Akt, PTEN, chromogranin A, survival
Full Text PDF
Address all correspondence to:
Herbert Chen, M.D., FACS
600 Highland Avenue
H4/750 Clinical Science Center
Madison, WI 53792-3284
Phone: 608-263-1387
Fax: 608-263-7652
Email: chen@surgery.wisc.edu
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