Impact of epidermal growth factor receptor and KRAS mutations on clinical outcome in resected non-small cell lung cancer patients.
OBJECTIVE
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.
Mark
M
Ragusa
Jacopo
J
Vannucci
Vienna
V
Ludovini
Fortunato
F
Bianconi
Stefano
S
Treggiari
Francesca R
FR
Tofanetti
Antonella
A
Flacco
Renato
R
Colella
Angelo
A
Sidoni
Lucio
L
Crinò
Francesco
F
Puma
D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking / Q000235:genetics; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins