Phenotype of bone metastases of non-small cell lung cancer: epidermal growth factor receptor expression and K-RAS mutational status

Abstract

Bone metastasis is a frequent complication of lung cancer progression, however, studies on bone metastatic tissues are scanty. Here we have collected a small cohort of 11 non-small cell lung cancer cases where primary tumors and corresponding bone metastases were available for pathological analysis. We have tested two molecular markers: EGFR protein expression and K-RAS mutation at codon 12 using immunohistochemistry and RFLPPCR, respectively. We have shown that using improved protocols, EGFR protein (both the extracellular as well as the cytoplasmic domain) is readily detectable in decalcified bone tissue. We found that the EGFR expression status is highly similar in bone metastases compared to the primary tumors, although the expression levels may change. Individual comparison of corresponding primary and metastatic NSCLC tissues indicated that downregulation of EGFR was a rare event (2/11) compared to upregulation (4/11) in bone metastases. On the other hand, our data indicate that the K-RAS mutational status of the primary tumor does not predict the status of the bone metastatic tissue of NSCLC, since we have observed both emergence of mutant clones in metastases from wild-type (wt) primary tumors and loss of mutant clones in metastases from mutant primaries in addition to the maintained mutant status. Our data support that at least two progression models occur in NSCLC, the samegene as well as the clonal selection one. It is noteworthy that in NSCLC cases with wt- or mutant KRAS, downregulation of EGFR expression was a rare event although upregulation in bone metastases was observed more frequently in wt K-RAS cases.