Zhejiang Key Laboratory of Radiation Oncology,Zhejiang Cancer Hospital,Hangzhou 310022,China (Tang HR,Hu X,Xu YJ,Dong BQ,Wang J,Kong Y,Ma HL,Zhang XQ,Chen M),Department of Pathology (Yang SF),Zhejiang Cancer Hospital,Hangzhou 310022,China;Zhejiang Cancer Research Institute,Zhejiang Cancer Hospital,Hangzhou 310022,China (Xu Q,Su D);Department of Thoracic/Head and Neck Medical Oncology,Division of Cancer Medicine,University of Texas M.D.Anderson Cancer Center,Houston,TX,7703,USA (Zhang JJ)
Abstract： Objective To conduct a large-scale survey of the epidermal growth factor receptor (EGFR) mutations among Chinese small cell lung cancer (SCLC) patients, and to analyze the genetic heterogeneity and clinical characteristics of EGFR mutations in primary SCLC. Methods From 2009 to 2014, tissue specimens were collected from a total of 557 patients with SCLC.A total of 45 surgery and 512 biopsy samples are included. Dideoxy sequencing was used to determine the EGFR mutations. The chi-square test was used to analyze the correlation between clinical variables and EGFR mutations. Survival analysis was performed using the Kaplan-Meier method. Multivariate prognostic analysis was made by the Cox model. Results In the 557 specimens, 38 had EGFR mutations (6.8%), containing 3 with E19 deletion, 3 with E21 L858R, 1 with E20 T790M, and others with non-classical mutations. There was no correlation of EGFR mutations with gender, age, or clinical stage. There was no significant difference in proportion of non-smokers between patients with and without EGFR mutations (11/36 vs. 86/398, P=0.080). After the patient-treatment history matching, patients with EGFR mutations had a significantly longer median overall survival time than those without EGFR mutations (24.43±9.46 vs. 14.17±0.84 months, P=0.020), indicating a better prognosis in patients with EGFR mutations. The Cox regression analysis suggested that limited stage disease, age of<65 years, and EGFR mutations were prognostic predictors (HR=2.610, 1.476,0.576, P=0.000,0.010,0.039). Conclusions EGFR mutations with high genetic heterogeneity can be found among the patients newly diagnosed with SCLC. EGFR mutations are positively correlated with the survival of patients with SCLC.
. Epidermal growth factor receptor mutations in primary small cell lung cancer:genetic heterogeneity and prognostic impacts[J]. Chinese Journal of Radiation Oncology, 2017, 26(3): 270-273.
[1] Paez JG,Jnne PA,Lee JC,et al. EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy[J].Science,2004,304(5676):1497-500.DOI:10.1126/science.1099314. [2] Morinaga R,Okamoto I,Furuta K,et al. Sequential occurrence of non-small cell and small cell lung cancer with the same EGFR mutation[J].Lung Cancer,2007,58(3):411-413.DOI:10.1016/j.lungcan.2007.05.014. [3] Zakowski MF,Ladanyi M,Kris MG,et al. EGFR mutations in small-cell lung cancers in patients who have never smoked[J].N Engl J Med,2006,355(2):213-215.DOI:10.1056/NEJMc053610. [4] Siegele BJ,Shilo K,Chao BH,et al. Epidermal growth factor receptor (EGFR) mutations in small cell lung cancers:two cases and a review of the literature[J].Lung Cancer,2016,95:65-72. DOI:10.1016/j.lungcan.2016.02.012. [5] George J,Lim JS,Jang SJ,et al. Comprehensive genomic profiles of small cell lung cancer[J].Nature,2015,524(7563):47-53.DOI:10.1038/nature14664. [6] Jiang LY,Huang JQ,Higgs BW,et al. Genomic landscape survey identifies SRSF1 as a key oncodriver in small cell lung cancer[J].PLoS Genet,2016,12(4):e1005895.DOI:10.1371/journal.pgen.1005895. [7] Takagi Y,Nakahara Y,Hosomi Y,et al. Small-cell lung cancer with a rare epidermal growth factor receptor gene mutation showing"wax-and-wane" transformation[J].BMC Cancer,2013,13(1):529.DOI:10.1186/1471-2407-13-529. [8] Asai N,Ohkuni Y,Matsuda M,et al. Small-cell lung cancer with epidermal growth factor receptor mutation:Case report and review of literature[J].Indian J Cancer,2014,51(3):384-385.DOI:10.4103/0019-509X.146753. [9] Le XN,Desai NV,Majid A,et al. De novo pulmonary small cell carcinomas and large cell neuroendocrine carcinomas harboring EGFR mutations:lack of response to EGFR inhibitors[J].Lung Cancer,2015,88(1):70-73.DOI:10.1016/j.lungcan.2015.02.003. [10] Kurahara Y,Kawaguchi T,Tachibana K,et al. Small-cell lung cancer in never-smokers:a case series with information on family history of cancer and environmental tobacco smoke[J].Clin Lung Cancer,2012,13(1):75-79.DOI:10.1016/j.cllc.2011.04.001. [11] Norkowski E,Ghigna MR,Lacroix L,et al. Small-cell carcinoma in the setting of pulmonary adenocarcinoma:new insights in the era of molecular pathology[J].J Thorac Oncol,2013,8(10):1265-1271.DOI:10.1097/JTO.0b013e3182a407fa. [12] Niederst MJ,Sequist LV,Poirier JT,et al. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer[J].Nat Commun,2015,6:6377.DOI:10.1038/ncomms7377. [13] Shiao TH,Chang YL,Yu CJ,et al. Epidermal growth factor receptor mutations in small cell lung cancer:a brief report[J].J Thorac Oncol,2011,6(1):195-198.DOI:10.1097/JTO.0b013e3181f94abb. [14] Lu HY,Sun WY,Chen B,et al. Epidermal growth factor receptor mutations in small cell lung cancer patients who received surgical resection in China[J].Neoplasma,2012,59(1):100-104.DOI:10.4149/neo_2012_013. [15] Bordi P,Tiseo M,Barbieri F,et al. Gene mutations in small-cell lung cancer (SCLC):results of a panel of 6 genes in a cohort of Italian patients[J].Lung Cancer,2014,86(3):324-328.DOI:10.1016/j.lungcan.2014.10.002. [16] Varghese AM,Zakowski MF,Yu HA,et al. Small-cell lung cancers in patients who never smoked cigarettes[J].J Thorac Oncol,2014,9(6):892-896.DOI:10.1097/JTO.0000000000000142. [17] Sun JM,Choi YL,Ji JH,et al. Small-cell lung cancer detection in never-smokers:clinical characteristics and multigene mutation profiling using targeted next-generation sequencing[J].Ann Oncol,2015,26(1):161-166.DOI:10.1093/annonc/mdu504. [18] Wakuda K,Kenmotsu H,Serizawa M,et al. Molecular profiling of small cell lung cancer in a Japanese cohort[J].Lung Cancer,2014,84(2):139-144.DOI:10.1016/j.lungcan.2014.02.013. [19] Gow CH,Chien CR,Chang YL,et al. Radiotherapy in lung adenocarcinoma with brain metastases:effects of activating epidermal growth factor receptor mutations on clinical response[J].Clin Cancer Res,2008,14(1):162-168.DOI:10.1158/1078-0432.CCR-07-1468. [20] Ntaskagiannis D,Gogou P,Murray S,et al. The effect of EGFR mutation status in the outcome of radiotherapy in patients with locally advanced non small cell lung cancer (NSCLC)[J].Ann Cancer Res,2015,2(1):1-6.
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