Surgery yields best results for non–small cell lung cancer (NSCLC) patients. Epidermal growth factor receptor (EGFR) and its downstream factor Kirsten rat sarcoma viral oncogene homolog (KRAS) are variably mutated in NSCLC. Such mutations predict clinical response to tyrosine kinase inhibitors. This study evaluated incidence and correlation of EGFR and KRAS mutations with clinicopathologic parameters and outcome in resected stage I to III NSCLC.
We analyzed the clinical characteristics and outcome data for 230 patients who underwent resection at our institution for stage I to III NSCLC. The tumors were assessed for both EGFR (exons 18 to 21) and KRAS (exons 2 and 3) mutations by nested polymerase chain reaction and sequenced in both sense and antisense direction. Kaplan-Meier estimates of overall survival and disease-free survival were calculated for clinical and biological variables using Cox model.
EGFR and KRAS mutations were detected in 22 (9.6%) and 39 (16.9%) patients, respectively. In the whole population, both EGFR and KRAS mutations were significantly correlated with adenocarcinoma (ADC). Overall, EGFR mutations were more frequent in women (P<0.0001) and in nonsmokers (P<0.0001). In the ADC/BAC group, KRAS mutations were more frequent in man (P<0.02) and EGFR mutations (exon 19 deletion and L858R) demonstrated a tendency towards worse disease-free survival (P=0.056). No difference in outcome was seen between patients harboring KRAS mutations compared with KRAS wild type.
EGFR and KRAS mutations are frequent in ADCs and are not prognostic factors for survival. EGFR mutations could be used to identify patients suitable for adjuvant treatment with targeted therapy resulting in potentially improved outcomes.
*Thoracic Surgery Unit
∥Institute of Pathological Anatomy and Histology, University of Perugia Medical School
†Medical Oncology Division, S. Maria della Misericordia Hospital
‡Department of Electronic and Information Engineering, University of Perugia, Perugia
§Thoracic Surgery Unit, S. Camillo Forlanini Hospital, Roma, Italy
Supported partly by a grant from the Italian Association forcer Research (AIRC) and from the Umbria Association Against Cancer (AUCC).
The authors declare no conflicts of interest.
Reprints: Vienna Ludovini, PhD, Medical Oncology Division, S. Maria della Misericordia Hospital, 1, G. Dottori street, Perugia 06132, Italy. E-mail: firstname.lastname@example.org.