Details

Autor(en) / Beteiligte

• 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

Titel

Phospho-Akt Expression Is Associated with a Favorable Outcome in Non–Small Cell Lung Cancer

Ist Teil von

• Clinical cancer research, 2005-04, Vol.11 (8), p.2930-2936

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2005

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.