Prognostic Implication of EGFR, KRAS, and TP53 Gene Mutations in a Large Cohort of Japanese Patients with Surgically Treated Lung Adenocarcinoma

• Published in: Journal of thoracic oncology 2009-01, Vol.4 (1), p.22-29, Article 22
• Main Authors: Kosaka, Takayuki, Yatabe, Yasushi, Onozato, Ryoichi, Kuwano, Hiroyuki, Mitsudomi, Tetsuya
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - secondary; Adenocarcinoma - surgery; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Cell Differentiation; Cohort Studies; EGFR; Female; Follow-Up Studies; Gene mutations; Humans; KRAS; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Middle Aged; Molecular Sequence Data; Mutation - genetics; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor, Epidermal Growth Factor - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Sequence Homology, Amino Acid; Smoking; Survival Rate; TP53; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0b013e3181914111

Although mutation of the epidermal growth factor receptor (EGFR) gene is predictive for the response to EGFR-tyrosine kinase inhibitor, its prognostic impact for patients without EGFR-tyrosine kinase inhibitor treatment remains controversial. We examined for EGFR, KRAS or TP53 mutations in a consecutive large cohort of patients with lung adenocarcinoma, and evaluated their prognostic impact. We analyzed 397 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection. Total ribonucleic acid was extracted and direct sequencing of each gene was performed after reverse transcription-polymerase chain reaction. We found that 196 patients (49%) had EGFR mutations. Of these, 83 were exon 19 deletions (42%) and 92 were L858R (47%). Univariate analysis showed that patients with EGFR mutations survived for a longer period than those without mutations (p = 0.0046). However, there was no difference in overall survival between the patients with exon 19 deletion and those with L858R (p = 0.4144). Patients with KRAS mutations or TP53 mutations tended to survive for a shorter period (p = 0.2183 and 0.0230, respectively). Multivariate analysis using the Cox proportional hazards model revealed that smoking status (p = 0.0310) and disease stage (p < 0.0001) were independent prognostic factors. However, none of the gene mutations was independent prognostic factors (EGFR, p = 0.3225; KRAS, p = 0.8500; TP53, p = 0.3191). EGFR, KRAS, and TP53 gene mutations were not independently associated with the prognosis for Japanese patients with surgically treated lung adenocarcinoma.