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Annals of Oncology Advance Access originally published online on October 11, 2005
Annals of Oncology 2005 16(12):1906-1914; doi:10.1093/annonc/mdi408
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© 2005 European Society for Medical Oncology

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

T. Dutu1,2, S. Michiels3, P. Fouret4, F. Penault-Llorca5, P. Validire6, S. Benhamou7, E. Taranchon4,8, L. Morat2, D. Grunenwald9, T. Le Chevalier1, L. Sabatier2 and J.-C. Soria1,2,*

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

* Correspondence to: Dr J.-C. Soria, Department of Medicine, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. Tel: +33-1-42-11-43-01; Fax: +33-1-42-11-52-30; E-mail: soria{at}igr.fr

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.

Key words: EGFR, immunohistochemistry, lung adenocarcinoma, never-smokers, pAKT


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