Phospho-Akt overexpression in non-small cell lung cancer confers significant stage-independent survival disadvantage.
OBJECTIVE
Akt is a signal transduction protein that plays a central role in inhibiting apoptosis in a variety of cell types including human cancer cells. In cell lines derived from human non-small cell lung cancers (NSCLCs), Akt has been shown to confer chemoresistance by inhibition of apoptosis in response to different chemotherapeutic agents including platinum-based agents, which are often the first-line therapy for NSCLCs. Only 20% to 30% of patients with NSCLC treated with chemotherapy have clinical evidence of response. The purpose of this study is to determine whether or not overexpression of activated Akt [i.e., phosphorylated Akt (pAkt)] is correlated with survival.


METHODS
We studied tumors from 61 patients with NSCLC in three tissue microarrays. All patients were followed for a period of 10 years or until death. The arrays were studied immunohistochemically with antibodies against pAkt, p53, and Ki-67.


RESULTS
There was a statistically significant difference in survival between the 14 patients with strong pAkt staining and the 47 patients with weak to absent pAkt staining both by log-rank (P = 0.0416) and Breslow analysis (P = 0.0446). Difference in survival time with respect to pAkt status was also statistically significant even after accounting for stage at diagnosis (P = 0.004). Neither p53 nor Ki-67 was a statistically significant prognostic factor.


CONCLUSIONS
Overexpression of pAkt is an independent prognostic factor. Additional studies of human NSCLCs are warranted to drive the development of targeted tumor-specific antineoplastic therapies.
David
Odile
O
Department of Pathology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA. odavid@tulane.edu
Jett
James
J
LeBeau
Helena
H
Dy
Grace
G
Hughes
Janet
J
Friedman
Mitchell
M
Brody
Arnold R
AR
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D016019:Survival Analysis
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt