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Objective: To investigate the gene mutation of EGFR and KRAS in Chinese patients with non-small cell lung cancer (NSCLC), and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency., Methods: EGFR mutation was detected in 120 patients and KRAS mutation in 104 patients with NSCLC in Peking Union Medical College Hospital from March 2009 to December 2010, and the correlation of the gene mutations with the clinicopathological features and EGFR-TKI efficiency was analyzed in the study., Results: EGFR mutation was detected in 44 of 120 (36.7%) patients with NSCLC, in which three types of EGFR gene mutations were found: deletion in exon 19, exon 21 L858R (2573T > G) and Exon 21 L861Q (2582T > A) mutations. There were 29(24.2%) patients with EGFR exon 19 deletion, 14 (11.7%) patients with EGFR exon 21 L858R mutation and one (0.8%) with EGFR exon 21 L861Q mutation in the patients. All the mutations were single point mutations, and no multiple points mutations detected. EGFR mutation rate of bronchioloalveolar carcinoma and adenocarcinoma were higher than that of non-adenocarcinoma (P = 0.009). EGFR mutation rate was higher in female patients or patients without smoking history than male patients or patients with smoking history (P = 0.014, P = 0.001, respectively) in NSCLC patients. EGFR mutation rate was higher in patients without smoking history or patients with well-differentiated carcinoma than patients with smoking history or patients with moderately-and poorly-differentiated carcinoma (P = 0.008, P = 0.018, respectively). There was no difference in prognosis and EGFR-TKI treatment response rate between EGFR mutation patients and EGFR wild-type patients. Nine (8.7%) patients with KRAS mutation were detected in 104 NSCLC patients. There were four types of KRAS gene mutations detected: KRAS Gly12Ala (GGT > GCT), KRAS Gly12Arg (GGT > CGT), KRAS Gly12Val (GGT > GTT) and KRAS Gly12Cys (GGT > TGT). There were 4 patients with Cys mutation, 2 with Arg mutation, 2 with Val mutation and 1 with multiple points mutation of both Cys and Arg in exon 12. No relationship was found between KRAS mutation and clinicopathological feature either in NSCLC or in adenocarcinoma. Prognosis was worse in patients with KRAS mutation than in wild-type patients (P = 0.008). No patient with both EGFR and KRAS mutation was detected., Conclusions: EGFR mutation rate is related with gender, smoking history and pathological type in NSCLC patients, and is also related with differentiation and smoking history in adenocarcinoma patients. And prognosis is worse in patients with KRAS mutation than that with wild type.

Objective: To investigate the detection technology and its clinical significance of the EGFR gene mutation in non-small cell lung cancer., Methods: DNA direct sequencing methods by PCR amplification were used to detect EGFR gene exons 18-21 mutation and to analyze its clinical pathological significance in 192 patients with non-small cell lung cancer., Results: 64 of the 192 cases presented with EGFR gene tyrosine kinase binding domain mutation (64/192, 33.3%), of which exon 19 deletion mutation rate was 60.9% (39/64), exon 21 alternative mutation rate was 39.1% (25/64), but exons 18 and 20 mutation was not found in this group of patients. EGFR gene mutation rate was 58.5%(24/41) in lung adenocarcinoma associated with bronchioloalveolar carcinoma differentiation, which was significantly higher than that of ordinary adenocarcinoma (37.9%, 33/87), squamous cell carcinoma (7.5%, 4/53), large cell carcinoma (1/5) and adenosquamous carcinoma (2/6, P<0.05). EGFR gene mutation rates in male patients (20.9%, 24/115), were significantly higher than in the females (51.9%, 40/77; P<0.01); non-smokers (50.0%, 57/114), significantly higher than that of smokers (9.0%, 7/78; P<0.01)., Conclusions: DNA direct sequencing method by PCR amplification is stable and reliable in detection of EGFR gene mutation in non-small cell lung cancer. It might provide a scientific basis for targeted therapy.

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.

Objective: To explore the relationship between the mutations of epidermal growth factor receptor (EGFR) gene and clinicopathological characteristics in patients with non-small cell lung cancers (NSCLC)., Methods: Paraffin-embedded tissue specimens were obtained from 1444 patients with NSCLC. The genomic DNA was extracted. Mutations of EGFR gene (exons 19 and 21) were detected by real-time PCR., Results: DNA was available in 1410 cases. Somatic mutations of the EGFR gene were identified in 401 cases (27.8%). Among patients with EGFR mutations, 41.4% (n=166) had del E746-A750 of exon19, 6.7% (n=27) had del L747-P753insS of exon 19, 50.3% (n=201) had L858R of exon 21, and 1.5% (n=6) had L861Q of exon 21. Woman, non-smoker and adenocarcinoma showed a higher percentage of EGFR mutation (43.2%, 37.6%, and 33.5%, respectively). However, there was no association among age, grades, lymph node metastasis, and TNM stages (P>0.05). The mutation rate of BAC subtype (61.3%, 19/31) and adenocarcinoma with BAC features (48.0%, 12/25) was significantly higher than that of conventional adenocarcinoma (32.4%, 336/1038). A further assess of the smoking status found a trend that the more increased smoking exposure, the lower the incidence of EGFR mutations. A multivariable analysis revealed that adenocarcinoma, never smoking, and female were independently associated with EGFR mutations (odds rations=3.381, 2.393, and 1.727, respectively)., Conclusions: The detection rate of EGFR mutation is higher in Chinese patients, especially in non-smoking female patients with adenocarcinoma. Real-time PCR is a sensitive and accurate method to detect the mutations of EGFR gene and can therefore provide useful information for clinical treatment.

The p53 gene has been implicated in the pathogenesis of lung cancer as a tumor suppressor gene. Aberrations of the p53 gene (exon 6-8) was examined in 34 surgical specimens of lung cancer with single-strand-conformation-polymorphism analysis of polymerase chain reaction products. Structural abnormalities of the p53 gene were observed in 30 tumor specimens (88.2%), i.e, in 10 of the 12 specimens with squamous cell carcinoma, 8 of the 10 with adenocarcinoma, all the 3 small cell carcinoma, the only one large cell carcinoma, all the 5 alveolar cell carcinoma and all the 3 adenosquamous carcinoma. The aberrations of the p53 gene were not limited to a particular histological type or clinical stage and were not associated with degree of differentiation or history of heavy smoking. It is suggested that high mutation rate of the p53 gene may participate in the genesis of lung cancer. In this study, multiple primer polymerase chain reaction method was applied to detect the human papillomavirus DNA (HPV DNA) in human lung cancer. Only 4 of these 34 specimens were HPV DNA positive, and they were all of squamous cell carcinoma, 3 of them had p53 mutation.