Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer
| Autor: | John G. Edwards, Duncan Stewart, Catherine M. Richardson, Daniel E.B. Swinson, Dipika Patel, J. Louise Jones, Amit Shah, Kenneth J. O'Byrne, Donna Richardson, William A. Swain |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Blotting Western Adenocarcinoma Protein Serine-Threonine Kinases Carcinoma Non-Small-Cell Lung Proto-Oncogene Proteins medicine Carcinoma Humans Phosphorylation Lung cancer Protein kinase B Survival analysis Cancer staging Aged Neoplasm Staging Aged 80 and over business.industry Middle Aged medicine.disease Prognosis Immunohistochemistry Survival Analysis Radiation therapy Oncology Multivariate Analysis Cancer research Carcinoma Squamous Cell Female business Proto-Oncogene Proteins c-akt |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 11(8) |
| ISSN: | 1078-0432 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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