[Relationship of epidermal growth factor receptor gene mutations, clinicopathologic features and prognosis in patients with non-small cell lung cancer].
OBJECTIVE
To investigate epidermal growth factor receptor (EGFR) gene mutations in exons 19 and 21 of patients with non-small cell lung cancer (NSCLC) and to analyze the relationship of EGFR mutations with clinicopathological features and prognosis.


METHODS
The EGFR gene exons 19 and 21 of paraffin-embedded tumor tissue were amplified by PCR, followed by direct sequencing in 282 surgically-removed specimens of NSCLC. The relationship of EGFR gene mutations in NSCLC with clinicopathological features and prognosis were analyzed.


RESULTS
EGFR mutations were detected in 120 of 282 (42.6%) patients with NSCLC. There were 61 cases of the mutations in exon 19 and 66 cases of the mutations in exon 21, including 7 cases of the mutations both in exons 19 and 21. Mutations were more frequently observed in women (55.2%, 53/96) than in men (36.0%, 67/186), in 51 to 60-years-old (51.3%, 39/76) than ≤50-years-old (30.4%, 21/69) and >60-years-old (43.8%, 60/137), in non-smokers (54.3%, 69/127) than smokers (32.9%, 51/155), there was negative correlation of EGFR mutations with smoking status (P=0.000, rs=-0.216). EGFR mutations were more frequently observed in adenocarcinomas (47.8%, 64/134), bronchiolo-alveolar carcinomas (73.0%, 27/37), adenosquamous carcinomas (7/9) than squamous cell carcinomas (23.6%, 17/72) and other types (16.7%, 5/30). The EGFR mutation rate in the well differentiated, the middle differentiated, the poorly differentiated and the undifferentiated was 55.7% (68/122), 50.8% (30/59), 22.7% (17/75), 19.2% (5/26) respectively, the incidences of EGFR mutations decreased with the degrading of differentiation, there was positive correlation of EGFR mutations with differentiation of lung cancer (P=0.000, rs=0.296). The patients with EGFR mutations had better prognosis than those with wild-type EGFR (P=0.027). There was no association of EGFR mutations with clinical TNM stage.


CONCLUSIONS
EGFR mutations occur frequently in females, non-smokers and adenocarcinomas, bronchioloalveolar carcinomas, and adenosquamous carcinomas. The patients with EGFR mutations have better prognosis. The results may offer a practical approach to select the patients who may benefit from anti-EGFR target therapy.
Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Miao-jing
MJ
Fan
Hai-gang
HG
Li
Zhi-qiang
ZQ
Lü
Hui-zhong
HZ
Zhang
Xi-ming
XM
Shen
D000230:Adenocarcinoma / Q000235:genetics; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018196:Carcinoma, Adenosquamous / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D005784:Gene Amplification; D018773:Genes, erbB-1; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods; D012737:Sex Factors; D012907:Smoking; D015996:Survival Rate
D066246:ErbB Receptors