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Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcome in Resected Non–Small Cell Lung Cancer Patients

Ragusa, Mark, MD, PhD*; Vannucci, Jacopo, MD*; Ludovini, Vienna, PhD; Bianconi, Fortunato, PhD; Treggiari, Stefano, MD§; Tofanetti, Francesca R., PhD; Flacco, Antonella, PhD; Colella, Renato, MD; Sidoni, Angelo, MD, PhD; Crinò, Lucio, MD; Puma, Francesco, MD, PhD*

American Journal of Clinical Oncology: August 2014 - Volume 37 - Issue 4 - p 343–349
doi: 10.1097/COC.0b013e31827a7e7a
Original Articles: Thoracic

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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:

© 2014 by Lippincott Williams & Wilkins, Inc