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

Authors' Affiliations: University Departments of ¹ Oncology, ² Thoracic Surgery, and ³ Pathology, University of Leicester, Leicester, United Kingdom and ⁴ Department of Oncology, St James's Hospital, Dublin, Ireland

Requests for reprints: Kenneth J. O'Byrne, HOPE Department, St James's Hospital, Dublin 8, Ireland. Phone: 353-1-4103546; Fax: 353-1-4103428; E-mail: obyrne{at}stjames.ie.

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.

Key Words: Protein serine-threonine kinases • Lung cancer • Molecular diagnosis and prognosis • New targets

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