Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer.
BACKGROUND
Several lines of laboratory evidence support a role of persistent activation of Akt pathway in oropharyngeal squamous cell carcinoma (OSCC) progression. Loss of phosphatase PTEN is one of the proposed mechanisms of Akt activation. We sought to determine the prognostic significance of Akt activation in a cohort of patients with OSCC as well as the association between phosphorylated (activated) Akt and PTEN levels.


METHODS
Using a novel system of in situ quantitative protein expression analysis (AQUA), we studied the protein expression levels of phosphorylated Akt (p-Akt) and PTEN on a tissue microarray. The array included 79 OSCCs with a mean follow-up of 36 months.


RESULTS
Patients with tumors expressing low tumor p-Akt levels had lower 5-year local recurrence rates (5% versus 38%). Additionally, these patients had improved 5-year overall survival rates (45% versus 27%). This survival effect was likely due to disease recurrence, as there was no difference in death without recurrence between low- and high-expressing groups. In adjusted analysis, tumor p-Akt expression was a strong predictor of local recurrence. A significant inverse relationship was found between nuclear p-Akt and nuclear PTEN: Tumors with high nuclear p-Akt had low nuclear PTEN and vice versa.


CONCLUSIONS
Akt activation in OSCC is associated with adverse patient outcome, indicating that Akt is a promising molecular target in OSCC. PTEN loss may be one of the mechanisms of Akt activation in OSCC.
Yu
Ziwei
Z
Department of Surgery, Yale Cancer Center, P.O. Box 208032, New Haven, CT 06520, USA.
Weinberger
Paul M
PM
Sasaki
Clarence
C
Egleston
Brian L
BL
Speier
William F
WF
Haffty
Bruce
B
Kowalski
Diane
D
Camp
Robert
R
Rimm
David
D
Vairaktaris
Eleftherios
E
Burtness
Barbara
B
Psyrri
Amanda
A
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009959:Oropharyngeal Neoplasms / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D040081:Protein Array Analysis / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human