Relationship between the Mutations of Epidermal Growth Factor Receptor Gene and k-ras Gene and the Clinicopathological Features of Non-small Cell Lung Cancers

  Objective  To investigate the relationship between the mutations of epidermal growth factor receptor(EGFR)gene, k-ras gene and clinicopathological characteristics in Chinese patients with non-small cell lung cancers (NSCLC).

  Methods  Tumor cells were collected by microdissection from paraffin embedded tumor specimens obtained from 170 patients with NSCLC. The genomic DNA was extracted.Mutations of EGFR gene (exons 18, 19, 20, and 21) and k-ras gene (codons 12 and 13) were detected by scorpions amplification refractory mutation system (Scorpions ARMS).

  Results  Somatic mutations were identified involving the tyrosine kinase domain of the EGFR gene in 84 patients (49.4%), which included in-frame deletions of exon 19 (n=39), point mutation of exon 21L858R (n=34), point mutation of exon 21L861Q (n=3), insertions mutations (n=4) and point mutation in exon 20 (n=2), and co-existence of T790M point mutation in exon 20 and L858R point mutations in exon 21 (n=2). k-ras mutations were identified in 14 patients (8.2%), among whom a single-amino-acid substitution in codon 12 were noted in all of them including 8 for 12CYS, 3 for 12ASP, and 3 for 12VAL. Simultaneously harbored EGFR and k-ras gene mutations were not observed in any single NSCLC specimen. Compared adenocarcinoma with non-adenocarcinoma, EGFR mutation rate was statistically significant (P < 0.001) and the former had higher mutation rate. Also, the relationship between EGFR mutations and various clinicopathological factors suggested that the EGFR mutations usually occurred in the female, non-smokers, smaller tumors (≤ 3 cm), and better differentiation. However, there was no association among age, gender, smoking, tumor size, histological types, differentiation grades, lymph node metastasis, pTNM stages and k-ras mutations (P > 0.05).

  Conclusions  The detection rate of EGFR mutation is remarkably higher in China than other countries, especially in non-smoking female patients with adenocarcinoma. The detection rate of k-ras mutation is very low, which is not associated with the clinical features such as gender and age. The efficacy and drug resistance of gefitinib is associated with the mutations of EGFR and k-ras gene. k-ras mutations does not coexist with EGFR mutations. Scorpions ARMS method is a rapid, sensitive, and accurate technology in detecting the mutations of EGFR gene and k-ras gene and can therefore provide useful information for clinical decision-making.