Increased phospho-AKT (Ser(473)) expression in bronchial dysplasia: implications for lung cancer prevention studies.
AKT, a downstream mediator of phosphatidylinositol 3'-kinase, is activated in non-small cell lung cancer (NSCLC), but we have not yet defined the stage of malignant transformation at which AKT is activated in the bronchial epithelium. We performed immunohistochemical analysis of activated AKT [phosphorylated (p)-AKT Ser(473)] in tissue specimens of normal bronchial epithelium, bronchial hyperplasia and squamous metaplasia ("reactive" epithelium), bronchial dysplasia, and NSCLC. Among NSCLC specimens, immunohistochemical findings were correlated with patient demographics, tumor stage, histology, and survival. We observed p-AKT expression in 12 of 44 (27.3%) normal bronchial biopsy specimens, 4 of 9 (44.4%) reactive epithelium specimens, 22 of 25 (88%) dysplastic specimens, and 25 of 76 (33%) NSCLC specimens. Among patients with resected early-stage or locally advanced NSCLC, p-AKT expression had no effect on tumor stage, histology, or survival. Of the histological groups examined, bronchial dysplasia specimens expressed p-AKT most frequently, supporting AKT activation as an early event in lung cancer progression. Given its role as a mediator of malignant transformation, p-AKT should be investigated as a potential target in future lung cancer prevention studies.
Tsao
Anne S
AS
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
McDonnell
Timothy
T
Lam
Stephen
S
Putnam
Joe B
JB
Bekele
Nebiyou
N
Hong
Waun Ki
WK
Kurie
Jonathan M
JM
D015415:Biomarkers / Q000032:analysis; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D001984:Bronchial Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001999:Bronchoscopy; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human