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.

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.