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  • Title: [Detection of epidermal growth factor receptor mutations in non-small-cell lung carcinoma by direct sequencing and correlations with clinicopathological characteristics and sample types].
    Author: Sun MH, Yang F, Shen L, Zhang L, Chen Y, Cai X, Zhu XL, Zhou XY.
    Journal: Zhonghua Bing Li Xue Za Zhi; 2011 Oct; 40(10):655-9. PubMed ID: 22321541.
    Abstract:
    OBJECTIVE: To retrospectively analyze epidermal growth factor receptor (EGFR) gene mutation frequencies and distribution characteristics in Chinese patients with non-small-cell lung carcinoma (NSCLC) by direct gene sequencing. METHODS: Clinical samples from 443 NSCLC patients were obtained for EGFR gene mutation analysis, including 299 surgical specimens, 59 core biopsies and 85 fine needle aspiration and pleural effusion cytology specimens. All samples were processed from paraffin embedded blocks and microdissection was performed to enrich tumor cells. PCR based direct gene sequencing was used to investigate tyrosine kinase domain coding region involving exon 18 through 21. RESULTS: (1) Among 443 samples, 193 mutations were detected in 189 patients (42.7%) and 4 patients possessed two mutations involving two different exons in their tumor samples. The percentage of mutations involving exon 18 to 21 were 2.0% (4/193), 48.7% (94/193), 6.7% (13/193) and 42.5% (82/193) respectively. (2) There was no significant correlation of EGFR mutation with age, however, mutation rate (50.9%, 54/106) of exon 21 in patients over median age 57 was higher than that of the younger patients (32.2%, 28/87; P<0.01). (3) EGFR mutation rate was remarkably higher in female patients (53.5%, 107/200) than in male patients (33.7%, 82/243; P<0.01). (4) Mutation rate in adenocarcinomas (46.5%, 161/346) was much higher than in squamous cell carcinomas (13.3%, 4/30) and poorly differentiated carcinomas (24.1%, 7/29; P<0.01, P<0.05), while the adenosquamous carcinomas shared a mutation rate similar to that of adenocarcinoma (7/13, P>0.05). (5) In surgical samples, core biopsies and cytological samples, the EGFR mutation detection rates were 49.5% (148/299), 35.6% (21/59) and 23.5% (20/85) respectively. The fine needle aspiration and cytological samples showed much lower EGFR mutation detection rates (23.5%, 20/85) than that of surgical samples (49.5%, 148/299; P<0.01). CONCLUSIONS: (1) Direct gene sequencing is a reliable and effective method for the detection of EGFR mutations in NSCLC, particularly for unknown EGFR mutations. (2) EGFR mutations are more frequent in female patients and patients with adenocarcinoma NSCLC, involving mainly exon 19 and 21. (3) The mutation distribution in exons of EGFR gene appears age-related. (4) Detection rate of EGFR mutation varies in different sample types. Small biopsy and fine needle aspiration specimens are valuable materials for analyzing EGFR mutation in NSCLC, although rare false negativity may occur using such samples.
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