EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features

Abstract

We aimed to reveal the true status of epidermal growth factor receptor (EGFR) mutations in Chinese patients with non-small cell lung cancer (NSCLC) after lung resections. EGFR mutations of surgically resected fresh tumor samples from 697 Chinese NSCLC patients were analyzed by Amplification Refractory Mutation System (ARMS). Correlations between EGFR mutation hotspots and clinical features were also explored. Of the 697 NSCLC patients, 235 (33.7%) patients had tyrosine kinase inhibitor (TKIs) sensitive EGFR mutations in 41 (14.5%) of the 282 squamous carcinomas, 155 (52.9%) of the 293 adenocarcinomas, 34 (39.5%) of the 86 adenosquamous carcinomas, one (9.1%) of the 11 large-cell carcinomas, 2 (11.1%) of the 18 sarcomatoid carcinomas, and 2 (28.6%) of the 7 mucoepidermoid carcinomas. TKIs sensitive EGFR mutations were more frequently found in female patients (p < 0.001), non-smokers (p = 0.047) and adenocarcinomas (p < 0.001). The rates of exon 19 deletion mutation (19-del), exon 21 L858R point mutation (L858R), exon 21 L861Q point mutation (L861Q), exon 18 G719X point mutations (G719X, including G719C, G719S, G719A) were 43.4%, 48.1%, 1.7% and 6.8%, respectively. Exon 20 T790M point mutation (T790M) was detected in 3 squamous carcinomas and 3 adenocarcinomas and exon 20 insertion mutation (20-ins) was detected in 2 patients with adenocarcinoma. Our results show the rates of EGFR mutations are higher in all types of NSCLC in Chinese patients. 19-del and L858R are two of the more frequent mutations. EGFR mutation detection should be performed as a routine postoperative examination in Chinese NSCLC patients.

An Analysis of EGFR Mutations among 1506 Cases of Non-Small Cell Lung Cancer Patients in Guangxi, China

“…In the cohort of this study, we demonstrate the rate of EGFR-TKIs sensitive mutation in NSCLCs is 35.7% (537/1506), a finding which is in accordance with a previous study in China [17]. However, the EGFR-TKIs sensitive mutation rate of 41.8% in lung adenocarcinoma is lower than the rate of 66.3% in a study with a cohort in Southern China [16], but much higher than the mutation rate of 7.5% in the study with a cohort of Northern European populations [27, 28].…”

“…There is no significant difference between 19-del and L858R ( p = 0.296).This result is in accordance with the study in a cohort of the Chinese population by Lai and coworkers[17]. However, this result is inconsistent with other studies that investigated a cohort of Caucasian[18, 37, 38].…”

“…The EGFR mutations showed a close relationship with clinical characteristics of patients with lung cancer and mainly appeared in non-smoking female patients with adenocarcinoma lung cancers [12–14]. The frequency of EGFR mutations have a wide variation worldwide, ranging from 31% to 66% in Asian patients [15–17] and 7.5% to 40% in Caucasians [18, 19]. …”

Significance of EGFR signaling pathway genetic alterations in radically resected non-small cell lung cancers from a Polish cohort. One institutional study

“…The rates of EGFR-and KRAS-mutated tumors among our ADC samples (14.1% and 20.3%, respectively) were similar to the values reported for non-Asian ADC patients [56,57], including the results of two large Polish multicenter studies [28,58]. Consistently with the data reported previously [28,33,[57][58][59][60][61], EGFR mutations were more common in women and never-smokers, and in well-or moderately differentiated ADCs. All the KRAS mutations that occurred in smokers were independent of tumor grade in contrast to the data reported by Dacic et al [57].…”

Oxidative DNA Damage Modulates Trinucleotide Repeat Instability Via DNA Base Excision Repair

“…This is because the extra covalent bond of cdPu stabilizes the glycosidic bond and prevents the lesion from being removed by DNA glycosylases and direct hydrolysis of damage (42,242,243) Trinucleotide repeats (TNRs) are highly polymorphic in human genome and can be expanded or deleted during DNA metabolisms including DNA replication, repair and transcription (71,132,133,(253)(254)(255)(256)(257). TNR expansion is associated with more than 40 neurodegenerative diseases such as Huntington's disease, myotonic dystrophy, fragile X syndrome, and Friedreich's ataxia (74,253,258).…”