Phospho-Akt expression is associated with a favorable outcome in non-small cell lung cancer

Shah, Amit, Swain, William A., Richardson, Donna, Edwards, John, Stewart, Duncan J., Richardson, Catherine M., Swinson, Daniel E. B., Patel, Dipika, Jones, J. Louise, & O'Byrne, Kenneth J. (2005) Phospho-Akt expression is associated with a favorable outcome in non-small cell lung cancer. Clinical Cancer Research, 11(8), pp. 2930-2936.

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Abstract

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables. Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037). These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC. © 2005 American Association for Cancer Research.

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ID Code: 65679
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: paraffin, protein kinase B, adult, aged, article, cancer grading, cancer staging, cancer surgery, cell nucleus, controlled study, correlation analysis, cytoplasm, densitometry, female, histopathology, human, human tissue, immunohistochemistry, immunolocalization, lung adenocarcinoma, lung non small cell cancer, lymph node metastasis, male, multivariate analysis, priority journal, prognosis, protein expression, protein phosphorylation, quantitative analysis, reproducibility, staining, tumor differentiation, Western blotting, Adenocarcinoma, Aged, 80 and over, Blotting, Western, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Humans, Lung Neoplasms, Middle Aged, Neoplasm Staging, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Survival Analysis
DOI: 10.1158/1078-0432.CCR-04-1385
ISSN: 1078-0432
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2005 American Association for Cancer Research
Deposited On: 06 Jan 2014 04:17
Last Modified: 29 Jan 2015 05:21

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