Document Detail

Diverse prognostic roles of Akt isoforms, PTEN and PI3K in tumor epithelial cells and stromal compartment in non-small cell lung cancer.
MedLine Citation:
PMID:  19846969     Owner:  NLM     Status:  MEDLINE    
AIM: By tissue microarray methodology, the expression of altered Akt isoforms, PTEN and PI3K and their prognostic significance in 335 non-small cell lung cancer (NSCLC) tumors were investigated. PATIENTS AND METHODS: Tumor tissue was sampled and immunohistochemically quantified in 335 tumors from stage I to IIIA NSCLC patients both from tumor epithelial cells and surrounding stromal tissue in resected specimens. Correlations were made with clinicopathological variables. In addition, the expression of these markers was compared to 20 lung tissue cores from patients without any history of malignancy. RESULTS: A significantly higher PTEN expression was observed in control tissue when compared with tumor (p=0.001). There was a significantly negative correlation between PI3K expression in control versus tumor tissue (p=0.001, r=-0.2). In univariate analyses, high tumor epithelial cell expression of non-phosphorylated Akt2 (p=0.014) was a positive prognostic indicator for disease-specific survival (DSS), while high tumor epithelial cell expression of p-Akt Thr(308) (p=0.045) was a negative prognosticator. High stromal expression of total Akt3 (p=0.0008) and total PI3K (p=0.0003) correlated with a good prognosis. In the multivariate analysis, tumor epithelial cell expression of p-Akt Thr(308) (p=0.0009) and Akt2 (p=0.004) and the stromal cell expression of Akt3 (p=0.0008) and PI3K (p=0.012) were independent prognostic factors for DSS. CONCLUSION: High expression of non-phosphorylated Akt2 and low expression of p-Akt Thr(308) in tumor epithelial cells are independent predictors of improved survival in patients with primary NSCLC. In stromal cells, high expression of total Akt3 and total PI3K are both favourable independent prognostic indicators.
Samer Al-Saad; Tom Donnem; Khalid Al-Shibli; Magnus Persson; Roy M Bremnes; Lill-Tove Busund
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  29     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-22     Completed Date:  2009-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4175-83     Citation Subset:  IM    
Institute of Medical Biology, University of Tromso, Norway.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / metabolism*
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung / enzymology*,  pathology
Epithelial Cells / enzymology,  pathology
Lung Neoplasms / enzymology*,  pathology
Middle Aged
Neoplasm Staging
PTEN Phosphohydrolase / metabolism*
Proportional Hazards Models
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction
Stromal Cells / enzymology,  pathology
Reg. No./Substance:
0/Isoenzymes; EC 3-Kinase; EC Proteins c-akt; EC protein, human; EC Phosphohydrolase

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