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Phosphorylation of Akt (Ser⁴⁷³) Predicts Poor Clinical Outcome in Oropharyngeal Squamous Cell Cancer

Departments of ¹ Surgery (Otolaryngology), ² Radiation Therapy, ³ Pathology, and ⁴ Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; ⁵ Department of Otolaryngology, Medical College of Georgia, Augusta, Georgia; Divisions of ⁶ Population Sciences and ⁷ Medical Sciences, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; and ⁸ Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Athens, Greece

Requests for reprints: Amanda Psyrri, Yale Cancer Center, P.O. Box 208032, New Haven, CT 06520. Phone: 203-737-2476; Fax: 203-785-7531. E-mail: diamando.psyrri{at}yale.edu

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. (Cancer Epidemiol Biomarkers Prev 2007;16(3):553–8)

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				Corrections Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 1042 - 1042. [Full Text] [PDF]