Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers.
BACKGROUND
Non-small-cell lung cancer arising in never-smokers is usually of adenocarcinoma subtype. The oncogenic pathway of such tumors is poorly understood. To better define the biological characteristics of these tumors, we have compared the expression of a panel of epidermal growth factor receptor (EGFR)-related biomarkers in lung adenocarcinomas from smokers versus those in never-smokers.


METHODS
Using immunohistochemical analysis, we retrospectively analyzed EGFR, pAKT, PTEN, Ki-67, p27 and hTERT expression in specimens from 190 patients with completely resected lung adenocarcinomas (43 never-smokers and 147 smokers). These analyses were performed on tissue microarrays.


RESULTS
EGFR expression was higher in tumors from smokers (P < 0.01), while pAKT was overexpressed mainly in tumors from never-smokers (P = 0.01). As expected, the tumors from smokers presented a higher expression of Ki-67 and a more frequent loss of expression of p27 (P < 0.01). In a multivariate model, two biological factors (p27 and Ki-67) and two clinical factors (age and sex) showed independent significant correlation with never-smoking status.


CONCLUSIONS
Lung adenocarcinomas in never-smokers have a very distinct immunohistochemical expression profile of EGFR-related biomarkers as compared with lung adenocarcinomas in smokers. High levels of EGFR and Ki-67 are observed in smokers, while never-smokers are characterized by high levels of pAKT and p27.
Dutu
T
T
Department of Medicine, Institut Gustave Roussy, Villejuif, France.
Michiels
S
S
Fouret
P
P
Penault-Llorca
F
F
Validire
P
P
Benhamou
S
S
Taranchon
E
E
Morat
L
L
Grunenwald
D
D
Le Chevalier
T
T
Sabatier
L
L
Soria
J-C
JC
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012189:Retrospective Studies; D012907:Smoking / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D019098:Telomerase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human