Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer

Ziwei Yu, Paul M. Weinberger, Clarence Sasaki, Brian L. Egleston, William F. Speier IV, Bruce Haffty, Diane Kowalski, Robert Camp, David Rimm, Eleftherios Vairaktaris, Barbara Burtness, Amanda Psyrri

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)553-558
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Oropharyngeal Neoplasms
Squamous Cell Neoplasms
Squamous Cell Carcinoma
Phosphorylation
Recurrence
Neoplasms
PTEN Phosphohydrolase
Proteins
Survival Rate
Survival

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Yu, Z., Weinberger, P. M., Sasaki, C., Egleston, B. L., Speier IV, W. F., Haffty, B., ... Psyrri, A. (2007). Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer. Cancer Epidemiology Biomarkers and Prevention, 16(3), 553-558. https://doi.org/10.1158/1055-9965.EPI-06-0121

Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer. / Yu, Ziwei; Weinberger, Paul M.; Sasaki, Clarence; Egleston, Brian L.; Speier IV, William F.; Haffty, Bruce; Kowalski, Diane; Camp, Robert; Rimm, David; Vairaktaris, Eleftherios; Burtness, Barbara; Psyrri, Amanda.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 16, No. 3, 01.03.2007, p. 553-558.

Research output: Contribution to journalArticle

Yu, Z, Weinberger, PM, Sasaki, C, Egleston, BL, Speier IV, WF, Haffty, B, Kowalski, D, Camp, R, Rimm, D, Vairaktaris, E, Burtness, B & Psyrri, A 2007, 'Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 16, no. 3, pp. 553-558. https://doi.org/10.1158/1055-9965.EPI-06-0121
Yu, Ziwei ; Weinberger, Paul M. ; Sasaki, Clarence ; Egleston, Brian L. ; Speier IV, William F. ; Haffty, Bruce ; Kowalski, Diane ; Camp, Robert ; Rimm, David ; Vairaktaris, Eleftherios ; Burtness, Barbara ; Psyrri, Amanda. / Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2007 ; Vol. 16, No. 3. pp. 553-558.
@article{4170997f086c4b1bb331c4c10b994572,
title = "Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer",
abstract = "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.",
author = "Ziwei Yu and Weinberger, {Paul M.} and Clarence Sasaki and Egleston, {Brian L.} and {Speier IV}, {William F.} and Bruce Haffty and Diane Kowalski and Robert Camp and David Rimm and Eleftherios Vairaktaris and Barbara Burtness and Amanda Psyrri",
year = "2007",
month = "3",
day = "1",
doi = "10.1158/1055-9965.EPI-06-0121",
language = "English (US)",
volume = "16",
pages = "553--558",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Phosphorylation of Akt (Ser473) predicts poor clinical outcome in oropharyngeal squamous cell cancer

AU - Yu, Ziwei

AU - Weinberger, Paul M.

AU - Sasaki, Clarence

AU - Egleston, Brian L.

AU - Speier IV, William F.

AU - Haffty, Bruce

AU - Kowalski, Diane

AU - Camp, Robert

AU - Rimm, David

AU - Vairaktaris, Eleftherios

AU - Burtness, Barbara

AU - Psyrri, Amanda

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34047247690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047247690&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-06-0121

DO - 10.1158/1055-9965.EPI-06-0121

M3 - Article

C2 - 17372251

AN - SCOPUS:34047247690

VL - 16

SP - 553

EP - 558

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 3

ER -