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  • Title: Frequency of EGFR and KRAS mutations in Japanese patients with lung adenocarcinoma with features of the mucinous subtype of bronchioloalveolar carcinoma.
    Author: Hata A, Katakami N, Fujita S, Kaji R, Imai Y, Takahashi Y, Nishimura T, Tomii K, Ishihara K.
    Journal: J Thorac Oncol; 2010 Aug; 5(8):1197-200. PubMed ID: 20661086.
    Abstract:
    INTRODUCTION: Adenocarcinoma of the lung, especially bronchioloalveolar carcinoma (BAC) and adenocarcinoma with BAC features (AWBF), is potentially sensitive to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs); however, the efficacy seems to differ between the histologic subtypes. Mucinous BAC and AWBF (MBAC/AWBF) are not particularly responsive to EGFR-TKIs compared with nonmucinous BAC/AWBF (N-MBAC/AWBF). This may be due to the rarity of EGFR mutations and high frequency of KRAS mutations in MBAC/AWBF in contrast to N-MBAC/AWBF. METHODS: One hundred ninety-one patients with adenocarcinoma of the lung underwent surgery at our institution. There were 59 patients (30%) diagnosed with BAC/AWBF; 20 had MBAC/AWBF (10%) and 39 had N-MBAC/AWBF (20%). We isolated 44 tissue specimens from these patients (20 consecutive cases of MBAC/AWBFs and 24 randomly chosen cases of N-MBAC/AWBFs as the control group), and we analyzed them for EGFR and KRAS mutations. We used the peptide nucleic acid-locked nucleic acid polymerase chain reaction clump method to detect EGFR mutations and conventional DNA sequencing to identify KRAS mutations. RESULTS: EGFR mutations were found in three of the 20 MBAC/AWBFs (15%) and in 14 of the 24 N-MBAC/AWBFs (58%) (p = 0.005). In addition, there were 14 KRAS mutations identified in the 20 MBAC/AWBFs (70%) and seven in the 24 N-MBAC/AWBFs (29%) (p = 0.0144). CONCLUSIONS: The incidence of EGFR mutation is low and that of KRAS mutation is frequent in MBAC/AWBFs. Conversely, the incidence of EGFR mutation is high and KRAS mutation is low in N-MBAC/AWBFs. Based on these findings, EGFR-TKIs may not be effective in patients with MBAC/AWBF.
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