[Detection of epidermal growth factor receptor gene mutations and its clinical significance in non-small cell lung cancers].

Department of Pathology, Affiliated Changhai Hospital of Second Military Medical University, Shanghai 200433, China.
Zhonghua bing li xue za zhi Chinese journal of pathology 10/2011; 40(10):671-4. DOI: 10.3760/cma.j.issn.0529-5807.2011.10.007
Source: PubMed


To investigate the detection technology and its clinical significance of the EGFR gene mutation in non-small cell lung cancer.
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.
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).
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.

1 Read
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mutation analysis of epidermal growth factor receptor (EGFR) is essential in determining the therapeutic strategy for lung adenocarcinoma. Immunohistochemical (IHC) staining with EGFR mutation-specific antibodies of del E746-A750 in exon 19 and L858R in exon 21 has been evaluated in resection specimens in a few studies but rarely in biopsy samples. A total of 169 cases (78 biopsies and 91 resected specimens) of lung adenocarcinoma with EGFR mutation status predefined by direct DNA sequencing were histologically examined, and IHC was performed using EGFR mutation-specific antibodies of del E746-A750 and L858R. The cases with positive results by IHC but negative results by direct DNA sequencing were examined by amplified refractory mutation system. Our results showed that the frequency of EGFR mutations for both E746-A750 deletion and L858R mutation was 38.5% (65/169) by DNA sequencing or amplified refractory mutation system and 34.3% (58/169) by IHC in lung adenocarcinomas. Based on molecular test results, the overall sensitivity, specificity, positive predictive value, and negative predictive value of IHC using these 2 antibodies in all (biopsy/resection) cases were 87.7% (80%/94.3%), 99.0% (97.9%/100%), 98.3% (96%/100%), and 92.8% (88.7%/96.6%), respectively. Lung adenocarcinomas with a predominant acinar, papillary, lepidic, or solid growth pattern more often harbor EGFR mutation of del E746-A750 or L858R. In conclusion, the immunostaining with EGFR del E746-A750 and L858R mutation antibodies is a reliable screening method with high specificity and sensitivity for identifying the EGFR mutation in both resected and biopsied lung adenocarcinomas.
    No preview · Article · Mar 2013 · Human pathology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study was conducted to investigate the mutation status of epidermal growth factor receptor (EGFR) and its association with clinical characteristics and tumor markers in non-small-cell lung cancer (NSCLC) patients from the Xinjiang Uygur Autonomous Region in China. We enrolled 51 cases of NSCLC patients who received radical surgical treatment in the First Affiliated Hospital of Xinjiang Medical University. Quantitative polymerase chain reaction was applied to detect exons 18, 19, 20 and 21 of the EGFR gene in tumor tissues. Multiple tumor markers, including carcinoembryonic antigen (CEA), were assessed preoperatively. The EGFR-positive rate was 49.02% (25/51), with a mutation rate of 8% (2/25) in exon 18, 52% (13/51) in exon 19, 40% (10/51) in exon 21 and no mutations in exon 20. The positive mutation rate in men and women was 37.5% (12/32) and 68.42%, respectively (13/19), with a statistically significantly higher rate in women (P<0.05). There were also statistically significant differences among adenocarcinoma, adenosquamous carcinoma and squamous cell carcinoma cases (P<0.05), while no statistically significant differences were observed in adenocarcinoma cases regarding degree of differentiation, lymph node metastasis and TNM stage (P>0.05). There was a statistically significant association between the EGFR gene mutation status and the preoperative serum CEA level (P<0.05). The mutation rate of the EGFR gene was 68.42% in female lung adenocarcinoma patients, which supports the application of targeted therapy in such cases. However, whether it is possible to obtain information regarding targeted therapy through measuring the level of serum CEA for NSCLC patients with unknown EGFR mutation status requires further investigation through related studies including a higher number of cases.
    Preview · Article · May 2015 · Molecular and Clinical Oncology