Annals of Oncology 20: 1257–1263, 2009
Published online 17 March 2009
The NER proteins are differentially expressed
in ever smokers and in never smokers
with lung adenocarcinoma
D. Planchard1,2, J. Domont1, E. Taranchon2, I. Monnet3, J. Tredaniel4, R. Caliandro5, P. Validire6,
B. Besse1, J.-C. Soria1,7& P. Fouret2,8*
1Medical Oncology and Translational Research, Institut de Cance ´rologie Gustave Roussy,Villejuif;2Medical Oncology, Institut de Cance ´rologie Gustave Roussy,Villejuif;
3Department of Pneumology Creteil, Intercommunal Hospital of Creteil, Creteil;4Department of Pneumology, Saint-Louis Hospital, Paris;5Department of Thoracic
Disease, Institut Mutualiste Montsouris, Paris;6Department of Pathology, Institut Mutualiste Montsouris, Paris;7Department of Medical Oncology, Institut Gustave
Roussy, Villejuif and8Department of Pathology, Institut de Cance ´rologie Gustave Roussy,Villejuif, France
Received 21 September 2008; revised 3 December 2008; accepted 5 December 2008
Background: The expression levels of excision repair cross-complementation group 1 (ERCC1), replication protein A
(RPA) and xeroderma pigmentosum group F (XPF) nucleotide excision repair proteins may be important in the
response to platin-based therapy in lung cancer patients. It is not known whether ERCC1, RPA and XPF expression
levels differ between ever smokers (ES) and never smokers (NS).
Patients and methods: ERCC1, RPA and XPF expression levels were immunohistochemically evaluated in 125
patients with resected lung adenocarcinoma (AC) and carefully reviewed smoking status.
Results: ERCC1 was correlated with XPF (P = 0.001), but not with RPA (P = 0.11). In the univariate analysis, ERCC1
and XPF levels were higher in NS compared with ES (P = 0.004 and P = 0.003, respectively). In the multivariate
analysis, the smoking status was predictive of the ERCC1 level [odds ratio (OR) 2.5, 95% confidence interval (CI)
1.03–6.2] after adjustment for variables linked to the smoking status, including age and the presence of
bronchioloalveolar (BAC) features. The smoking status was also predictive of both RPA (OR 6.7, 95% CI 1.5–33.3) and
XPF levels (OR 12.5, 95% CI 2.9–50) after adjusting for age, sex and BAC features.
Conclusion: In patients with resected lung AC, ERCC1, RPA and XPF expression levels are higher in NS compared
Key words: ERCC1, immunohistochemistry, lung adenocarcinoma, NER, never smoker
About 90% of lung cancer deaths are caused by tobacco
smoking . Adenocarcinoma (AC) is the most common type
of lung cancer and the least strongly associated with smoking.
Over the last several decades, its incidence has increased in
relation to other histological types. Although cigarette smoking
is the main risk factor for lung cancer, lung cancer in never
smokers (NS) ranks as the seventh most common cause of
cancer death worldwide, ahead of cancer of the cervix, pancreas
and prostate .
Exposure to tobacco smoke carcinogens is directly
responsible for gene alterations seen in lung cancer. Striking
differences between ever smokers (ES) and NS have been
found in the mutation rate in the three major genes EGFR,
KRAS and TP53 that are involved in the pathogenesis of
lung cancers. These differences suggest that lung cancer arises
via different molecular mechanisms in NS compared with
ES. The TP53 mutational signature (ratio of transitions,
transversions and deletions) and the mutational spectrum
(distribution of mutations along the gene) are distinct in
lung cancers in ES and NS . Mutations in EGFR have
emerged as a frequent molecular alteration in lung cancer in
NS [3, 4]. Furthermore, EGFR and KRAS mutations exhibit
a mutually exclusive distribution . Epigenetic changes
such as DNA methylation differ in NS from those described
in ES and more specifically in p16, hMLH1 and hMSH2 [6,
7]. Also, chromosomal aberrations in lung cancer have
been described as possibly different in NS and in
Platinum-based chemotherapy has been used to treat a wide
variety of solid tumours including lung, head and neck,
ovarian, cervical and testicular cancer for over three decades
. Many patients eventually relapse following treatment and
become refractory to these anticancer agents .
Chemotherapy failure is mainly due to drug resistance in
tumour cells. Recent studies have reported that the DNA repair
*Correspondence to: Dr P. Fouret, Department of Translational Research, Institut
de Cance ´rologie Gustave Roussy, 94805 Villejuif Cedex, France. Tel: +33-142116510;
Fax: +33-142116094; E-mail: email@example.com
ª The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: firstname.lastname@example.org
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Annals of Oncology
Volume 20|No. 7|July 2009 doi:10.1093/annonc/mdn785 | 1263
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