Analysis of gene detection status of EGFR mutation in 170 patients with advanced lung adenocarcinoma

doi:10.3760/cma.j.issn.1673-422X.2019.01.003

Abstract

Abstract: Objective To explore and analyze the actual use of different detection methods and samples in detection of epidermal growth factor receptor (EGFR) mutation in patients with advanced lung adenocarcinoma. Methods The clinical data of 170 patients with advanced lung adenocarcinoma receiving EGFR gene detection in Department of Respiratory Medicine of Nanjing Chest Hospital were collected and an analysis of initial result and continuous detection conditions was made. Results The EGFR sensitive mutation rate of the first detection in 170 patients was 49.4% (84/170). The detection rate of EGFR sensitive mutation in female patients was higher than that in male patients ［61.4% (43/70) vs. 41.0% (41/100); χ2=6.875, P=0.009］. The detection rate of EGFR sensitive mutation in patients aged 65 or older was lower than that in patients younger than 65 years old ［41.6% (47/113) vs. 64.9% (37/57); χ2=8.242, P=0.004］. The detection rate of EGFR sensitive mutation in smokers was lower than that in nonsmokers ［34.3% (24/70) vs. 60.0% (60/100); χ2=10.892, P=0.001］. A total of 60 patients were retested after disease progression, and the detection rate of T790M was 48.3% (29/60). The detection rate of EGFR sensitive mutation in the initial examination in 170 patients: tumor tissue (biopsy and pleural effusion cell wax block) for 50.8% (64/126), ctDNA (pleural effusion and peripheral blood) for 45.5% (20/44), with no significant difference (χ2=0.372, P=0.542); PCR method for 51.0% (77/151), nextgeneratio sequencing (NGS) method for 36.8% (7/19), with no significant difference (χ2=1.352, P=0.245). The detection rate of T790M in 60 patients receiving drug resistance: PCR method for 51.9% (14/27), NGS method for 45.5% (15/33), with no significant difference (χ2=0.243, P=0.622). The use of tumor tissue was 74.1% (126/170) in the initial examination, and ctDNA accounted for 25.9% (44/170). The use of tumor tissue was 11.7% (7/60) in the second examination, and ctDNA accounted for 88.3% (53/60). The use of tumor tissue was 23.1% (3/13) in the third examination, and ctDNA accounted for 76.9% (10/13). The proportions of detection methods used for the 3 tests were as follows, the first test: PCR accounted for 88.8% (151/170), and NGS accounted for 11.2% (19/170); the second test: PCR accounted for 45.0% (27/60), and NGS accounted for 55.0% (33/60); the third test: NGS accounted for 100% (13/13). Conclusion For patients with advanced lung adenocarcinoma, making full use of different tumor specimens and ctDNA helps improving the detection rate of EGFR mutation, and reasonable use of PCR technology and NGS method can bring maximum benefits to patients.

Key words: Lung neoplasms, Adenocarcinoma, Receptor, epidermal growth factor, Mutation, Laboratory techniques and procedures

Hu Wei, Zhang Yu. Analysis of gene detection status of EGFR mutation in 170 patients with advanced lung adenocarcinoma[J]. Journal of International Oncology, 2019, 46(1): 11-16.

References

［1］ Jemal A, Bray F, Center MM, et al. Global cancer statistics［J］. CA Cancer J Clin, 2011, 61(2): 69-90. DOI: 10.3322/caac.20107. ［2］梁智勇, 周晓燕. 中国非小细胞肺癌患者表皮生长因子受体基因突变检测专家共识（2016版）［J］. 中华病理学杂志, 2016, 45(4): 217-220. DOI: 10.3760/cma.j.issn.0529-5807.2016.04.001. ［3］ Normanno N, Denis MG, Thress KS, et al. Guide to detecting epidermal growth factor receptor (EGFR) mutations in ctDNA of patients with advanced nonsmallcell lung cancer［J］. Qncotarget, 2017, 8(7): 12501-12516. DOI: 10.18632/oncotarget.13915. ［4］ Hasegawa T, Sawa T, Futamura Y, et al. Feasibility of rebiopsy in nonsmall cell lung cancer treated with epidermal growth factor receptortyrosine kinase inhibitors［J］. Intern Med, 2015, 54(16): 1977-1980. DOI: 10.2169/internalmedicine.54.4394. ［5］ Yatabe Y, Kerr KM, Utomo A, et al. EGFR mutation testing practices within the Asia Pacific region: results of a multicenter diagnostic survey［J］. Thorac Oncol, 2015, 10(3): 438-445. DOI: 10.1097/JTO.0000000000000422. ［6］ Huang WL, Wei F, Wong DT, et al. The emergent landscape of detecting EGFR mutations using circulating tumor DNA in lung cancer［J］. Biomed Res Int, 2015, 2015: 340732. DOI: 10.1155/2015/340732. ［7］ Sun W, Yuan X, Tian Y, et al. Noninvasive approaches to monitor EGFR-TKI treatment in nonsmallcell lung cancer［J］. J Hematol Oncol, 2015, 8: 95. DOI: 10.1186/s1304501501936. ［8］张美玲, 李春, 叶茂松, 等. 改良Blocker PCR检测EGFRTKI耐药后非小细胞肺癌血浆EGFR T790M突变的价值［J］. 复旦学报（医学版）, 2018, 45(1): 45-51. DOI: 10.3969/j.issn.1672-8467.2018.01.007. ［9］ Yeo CD, Kim JW, Kim KH, et al. Detection and comparison of EGFR mutations in matched tumor tissues, cell blocks, pleural effusions, and sera from patients with NSCLC with malignant pleural effusion, by PNA clamping and direct sequencing ［J］. Lung Cancer, 2013, 81(2): 207-212. DOI: 10.1016/j.lungcan.2013.04.023. ［10］ Aisner DL, Deshpande C, Baloch Z, et al. Evaluation of EGFR mutation status in cytology specimens: an institutional experience［J］. Diagn Cytopathol, 2013, 41(4): 316-323. DOI: 10.1002/dc.21851. ［11］ Goto K, Ichinose Y, Ohe Y, et al. Epidermal growth factor receptor mutation status in circulating free DNA in serum: from IPASS, a phase Ⅲ study of gefitinib or carboplatin/paclitaxel in nonsmall cell lung cancer［J］. J Thorac Oncol, 2012, 7(1): 115-121. DOI: 10.1097/JTO.0b013e3182307f98. ［12］ Douillard JY, Ostoros G, Cobo M, et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: circulatingfree tumor DNA as a surrogate for determination of EGFR Status［J］. J Thorac Oncol, 2014, 9(9): 13451353. DOI: 10.1097/JTO.0000000000000263. ［13］ Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early and latestage human malignancies［J］. Sci Transl Med, 2014, 6(224): 224ra24. DOI: 10.1126/scitranslmed. 3007094. ［14］ Yu HA, Arcila ME, Rekhtman N, et al. Analysis of tumor specimens at the time of acquired resistance to EGFRTKI therapy in 155 patients with EGFRmutant lung cancers［J］. Clin Cancer Res, 2013, 19(8): 2240-2247. DOI: 10.1158/1078-0432.CCR-12-2246. ［15］ Thess KS, Brant R, Carr TH, et al. EGFR mutation detection in ctDNA from NSCLC patient plasma: a crossplatform comparison of leading technologies to support the clinical development of AZD9291［J］. Lung Cancer, 2015, 90(3): 509-515. DOI: 10.1016/j.lungcan.2015.10.004. ［16］ John T, Bowden JJ, Clarke S, et al. Australian recommendations for EGFR T790M testing in advanced nonsmall cell lung cancer［J］. Asia Pac J Clin Oncol, 2017, 13(4): 296-303. DOI: 10.1111/ajco.12699.

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