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Annals of Oncology Advance Access published online on March 8, 2006
Annals of Oncology, doi:10.1093/annonc/mdl038
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© 2006 European Society for Medical Oncology
Received December 8, 2005
Revised February 1, 2006
Accepted February 3, 2006

original article

Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors

A. Italiano 1 *, F. Burel Vandenbos 2, J. Otto 3, J. Mouroux 4, D. Fontaine 5, P.-Y. Marcy 3, N. Cardot 2, A. Thyss 3, and F. Pedeutour 6

1 Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France; Laboratory of Solid Tumors Genetics, Centre Hospitalier Universitaire de Nice and CNRS UMR 6543, Faculté de Médecine, Canceropôle PACA, Nice, France
2 Department of Pathology, Centre Hospitalier Universitaire de Nice, Nice, France
3 Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France
4 Department of Thoracic Surgery, Centre Hospitalier Universitaire de Nice, Nice, France
5 Department of Neurosurgery, Centre Hospitalier Universitaire de Nice, Nice, France
6 Laboratory of Solid Tumors Genetics, Centre Hospitalier Universitaire de Nice and CNRS UMR 6543, Faculté de Médecine, Canceropôle PACA, Nice, France

* To whom correspondence should be addressed.
A. Italiano, E-mail: antoineitaliano{at}cario.fr


  Abstract

Background: Very recent studies have suggested that EGFR gene copy number and expression obtained by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) should be used to predict which lung cancer patients are expected to respond to anti-EGFR treatments. However, it is still not known whether EGFR expression differs in metastases compared to primary non-small cell lung cancer (NSCLC).

Patients and methods: EGFR status was analysed by IHC and FISH on tumor samples of primary NSCLC and at least one distant metastatic lesion in 30 patients.

Results: Ten cases (33.3%) showed primary tumor/metastasis discordance by IHC analysis (n = 30): in seven cases, EGFR was expressed in the primary tumor but not in the metastasis, while three samples showed EGFR expression in the metastasis but not in the primary tumor (Pearson correlation coefficient = 0.331, P = 0.0074). By FISH (n = 26), seven (27%) cases were discordant: six cases showed a high-level of EGFR polysomy in the primary tumor but not in the metastasis and one case showed a high-level of EGFR polysomy in the metastasis but not in the primary sample (Pearson correlation coefficient = 0.52, P = 0.007).

Conclusion: EGFR expression is not stable during metastatic progression in a significant proportion of NSCLC. These findings have to be considered in future prospective studies.

Keywords: epidermal growth factor receptor; non small cell lung cancer; EGFR inhibitor.
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