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Annals of Oncology Advance Access published online on October 11, 2005
Annals of Oncology, doi:10.1093/annonc/mdi408
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© 2005 European Society for Medical Oncology
Received July 1, 2005
Revised July 28, 2005
Accepted August 2, 2005

Original article

Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers

T. Dutu 1, S. Michiels 2, P. Fouret 3, F. Penault-Llorca 4, P. Validire 5, S. Benhamou 6, E. Taranchon 7, L. Morat 8, D. Grunenwald 9, T. Le Chevalier 10, L. Sabatier 8, and J.-C. Soria 1*

1 Department of Medicine, Institut Gustave Roussy, Villejuif, France; Department of Laboratoire de Radiobiologie et Oncologie, Commissariat à l'Energie Atomique, Fontenay aux Roses, France
2 Department of Biostatistics, Institut Gustave Roussy, Villejuif, France
3 Department of Translational Research Unit, Institut Gustave Roussy, Villejuif, France
4 Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France
5 Department of Pathology, Institut Mutualiste Montsouris, Paris, France
6 CNRS UPR2169, Institut Gustave Roussy, Villejuif, France
7 Department of Translational Research Unit, Institut Gustave Roussy, Villejuif, France; Department of Pathology, Institut Gustave Roussy, Villejuif, France
8 Department of Laboratoire de Radiobiologie et Oncologie, Commissariat à l'Energie Atomique, Fontenay aux Roses, France
9 Department of Thoracique, Institut Mutualiste Montsouris, Paris, France
10 Department of Medicine, Institut Gustave Roussy, Villejuif, France

* To whom correspondence should be addressed.
J.-C. Soria, E-mail: soria{at}igr.fr


  Abstract

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.

Patients and 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.

Keywords: EGFR; immunohistochemistry; lung adenocarcinoma; never-smokers; pAKT.
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