Impact of KRAS and EGFR Gene Mutations on Recurrence and Survival in Patients with Surgically Resected Lung Adenocarcinomas

• Published in: Annals of surgical oncology 2012-07, Vol.19 (Suppl 3), p.347-354
• Main Authors: Sonobe, Makoto, Kobayashi, Masashi, Ishikawa, Masashi, Kikuchi, Ryutaro, Nakayama, Ei, Takahashi, Tsuyoshi, Menju, Toshi, Takenaka, Kazumasa, Miyahara, Ryo, Huang, Cheng-Long, Okubo, Kenichi, Bando, Toru, Date, Hiroshi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Codon; Disease-Free Survival; Exons; Female; Genes, Neoplasm; Humans; Kaplan-Meier Estimate; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Medicine; Medicine & Public Health; Middle Aged; Mutagenesis, Insertional; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - therapy; Oncology; Point Mutation; Proportional Hazards Models; Protein Kinase Inhibitors - administration & dosage; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Retrospective Studies; Sequence Deletion; Surgery; Surgical Oncology; Time Factors; Translational Research and Biomarkers
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-011-1799-8

Background Oncogenic gene mutations observed in lung adenocarcinomas, such as epidermal growth factor receptor ( EGFR ) and KRAS , have some predictive value for chemotherapeutic drugs or EGFR–tyrosine kinase inhibitors. However, the influence of these gene alterations on patients’ prognosis remains controversial. Methods We retrospectively analyzed the tumors of 180 patients with completely resected pathological stage I–III lung adenocarcinoma which harbored either KRAS codon 12 mutation or EGFR gene mutations within exons 18–21 to investigate the impact of these gene mutations on the patients’ survival. Gene mutations were detected by established methods. Results Of 180 patients, 32 had KRAS codon 12 mutations (KRAS group), 148 had EGFR mutations within exon 18–21 (EGFR group). Pathological stage and operation mode were independent factors for disease-free survival. However, the EGFR group had better overall survival than the KRAS group ( P  = 0.0271). Cox proportional hazard model revealed pathological stage ( P  = 0.0001) and presence of EGFR gene mutations ( P  = 0.0408) were independent factors for overall survival. In survival after tumor recurrence, the EGFR group had a better median survival time (46.7 months) after recurrence than the KRAS group (26.0 months). Conclusions In patients with completely resected lung adenocarcinomas, KRAS and EGFR gene mutation status of tumors was not associated with disease-free survival. However, the presence of an EGFR gene mutation boded well for the patient’s overall survival, and thus patients with EGFR mutations have a better prognosis than those with KRAS mutations.