|Table of Contents|

Clinicopathological characteristics analysis of non-small cell lung cancer patients with concomitant EGFR mutation and ALK fusion

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 24
Page:
4616-4623
Research Field:
Publishing date:

Info

Title:
Clinicopathological characteristics analysis of non-small cell lung cancer patients with concomitant EGFR mutation and ALK fusion
Author(s):
ZHAO Xilian1; DING Caixia1; YU Xueyan1; WANG Xiaomin1; GUO Yu1; ZHANG Juan1; HAN Le2; CHEN Wenjuan3; HAN Xiuping4
1.Department of Pathology;2.Department of Thoracic Surgery;3.Department of Oncology,Shaanxi Provincial Cancer Hospital,Shaanxi Xi'an 710061,China;4.Cardiology and Cerebrovascular Hospital,Yan'an University Affiliated Hospital,Shaanxi Yan'an 716000,China.
Keywords:
non-small cell lung cancer; epithelial growth factor receptor（EGFR）; anaplastic lymphoma kinase（ALK）; concomitant
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2024.24.006
Abstract:
Objective：To investigate the frequency of non-small cell lung cancer patients with concomitant EGFR mutation and ALK fusion and its relationship with clinicopathological features.Methods：From 2016 to 2021,we collected data from 2 028 patients diagnosed with non-small cell lung cancer at our hospital.The expression of ALK (Ventana-D5F3) protein was detected by immunohistochemistry,and mutations in the EGFR and ALK genes were detected using fluorescence PCR.Co-mutants were analyzed by NGS sequencing.Results：There were a total of 8 cases with concomitant EGFR mtation and ALK fusion，accounting for 0.39%(8/2 028).There were 7 females and 1 male,with an average age of 56 years (range:35 to 69).Seven patients had no smoking history,and 1 patient did.Clinical stages were as follows:1 case in stage II,1 case in stage III,and 6 cases in stage IV.The histological type was adenocarcinoma.PCR detection showed that EGFR exon 19 deletion mutations were found in 5 cases (62.5%),EGFR exon 21 L858R mutations in 2 cases (25%),and EGFR exon 20 S768I mutation in 1 case (12.5%),with ALK fusion.Immunohistochemical analysis of ALK protein expression in 8 cases.Among them,there were 4 cases of NGS sequencing,all of which were EML4-ALK fusion,and the common fusion type was E13:A20.One case involved synchronous multiple primary lung cancer.Seven patients were treated with TKIs at different times.Three patients received epidermal growth factor receptor tyrosine kinase inhibitors,PD.Two patients received ALK tyrosine kinase inhibitors,PR.In one case,dual therapy targeting both EGFR and ALK was used simultaneously,PD.One case was treated with EGFR first and ALK-TKIs later,PR.The survival time was 5~81 months,of which 3 cases were still alive.Conclusion：EGFR and ALK driver gene dual mutations in lung cancer are rare in clinical practice,but are more common in women,non-smokers,and advanced lung adenocarcinoma.Common mutations are the main types of co-mutants,and it responds well to ALK-TKIs treatment.For newly diagnosed non-small cell lung cancer,especially lung adenocarcinoma patients,it is recommended to perform multi-gene and multi-platform testing to obtain more genetic mutation information and provide a basis for personalized treatment.

References:

［1］国家卫生健康委办公厅.原发性肺癌诊疗指南（2022年版）［J］.协和医学杂志,2022,13(04):549-570. General Office of National Health Commission of the People's Republic of China.Clinical Practice Guideline for Primary Lung Cancer(2022 version)［J］.Medical Journal of Peking Union Medical College Hospital,2022,13(04):549-570.
［2］LINDEMAN NI,CAGLE PT,AISNER DL,et al.Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors:guideline from the college of American pathologists,the international association for the study of lung cancer,and the associationfor molecular pathology［J］.Arch Pathol Lab Med,2018,142(3):321-346.
［3］GAINOR JF,VARGHESE AM,OU SH,et al.ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS:an analysis of 1,683 patients with non-small cell lung cancer［J］.Clin Cancer Res,2013,19(15):4273-4281.
［4］ZHAO Y,WANG S,ZHANG B,et al.Clinical management of non-small cell lung cancer with concomitant EGFR mutations and ALK rearrangements:efficacy of EGFR tyrosine kinase inhibitors and crizotinib［J］.Target Oncol,2019,14(2):169-178.
［5］王鑫,钟殿胜.非小细胞肺癌EGFR和ALK基因双突变研究进展［J］.中国肺癌杂志,2018,21(09):686-691. WANG X,ZHONG DS.Advances in double mutations of EGFR and ALK gene in non-small cell lung cancer［J］.Chin J Lung Cancer,2018,21(09):686-691.
［6］吴丹,李静，姚梅宏，等.非小细胞肺癌表皮生长因子受体、间变性淋巴瘤激酶、ROS1基因突变及突变共存的临床病理学意义［J］.中华病理学杂志,2021,50(03):251-253. WU D,LI J,YAO MH,et al.Clinicopathological significance in non-small cell lung cancer with mutations and co-mutations of EGFR,ALK and ROS1［J］.Chinese Journal of Pathology,2021,50(03):251-253.
［7］夏丹丹,王惠宇,刘超英，等.EGFR突变和EML4-ALK重排双阳性非小细胞肺癌研究进展［J］.国际呼吸杂志,2019,39(04):300-306. XIA DD,WANG HY,LIU CY,et al.Research progress in NSCLC with co-existence of EGFR mutation and EML4-ALK rearrangement［J］.Int J Respir,2019,39(04):300-306.
［8］MOHAPATRA PR,SAHOO S,BHUNIYA S,et al.Concomitant echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in non-small cell lung cancer patients from eastern India［J］.J Cancer Res Ther,2020,16(4):850-854.
［9］LO RUSSO G,IMBIMBO M,CORRAO G,et al.Concomitant EML4-ALK rearrangement and EGFR mutation in non-small cell lung cancer patients:a literature review of 100 cases［J］.Oncotarget,2017,8(35):59889-59900.
［10］ZHONG WX,WEI XF.Coexistence of anaplastic lymphoma kinase rearrangement in lung adenocarcinoma harbouring epidermal growth factor receptor mutation:A single-center study［J］.World J Clin Cases,2022,10(33):12164-12174.
［11］孔君,杨雪,孔辉,等.2394例肺腺癌患者EGFR及ALK驱动基因分析［J］.南京医科大学学报(自然科学版),2020,40(05):675-680,719. KONG J,YANG X,KONG H,et al.Analysis of EGFR and ALK oncogenic drivers in 2394 patients with lung adenocarcinoma ［J］.Journal of Nanjing Medical University(Natural Sciences),2020,40(05):675-680,719.
［12］左安欣,张晓妹,仇玮.非小细胞肺癌患者肿瘤组织中驱动基因的分子病理检测分析及其临床意义［J］.现代医药卫生,2022,38(07):1139-1143. ZUO AX,ZHANG XM,QIU W.Molecular pathological detection and analysis of the driver genes in tumor tissues of the patients with non-small cell lung cancer and its clinical significance［J］.J Mod Med Health,2022,38(07):1139-1143.
［13］中国非小细胞肺癌ALK检测模式真实世界多中心研究专家组,中华医学会病理学分会分子病理学组.中国非小细胞肺癌ALK检测临床实践专家共识［J］.中华病理学杂志,2019,48(12):913-920. Experts from the RATICAL Study (ALK Testing in Chinese Advanced Non-Small Cell Lung Cancer Patients:A National-Wide Multicenter Prospective Real World Data Study)，Molecular Pathology Committee of Chinese Society of Pathology．Expert consensus on clinical practice of ALK fusion detection in non-small cell lung cancer in China［J］.Chinese Journal of Pathology,2019,48(12):913-920．
［14］中华医学会病理学分会,国家病理质控中心,中华医学会肿瘤学分化肺癌学组.非小细胞肺癌分子病理检测临床实践指南(2021版)［J］.中华病理学杂志,2021,50(04):323-332. Chinese Society of Pathology,Pathology Quality Control Center,Chinese Medical Association Chinese Society of Oncology.Guidelines on clinical practice of molecular tests in non-small cell lung cancer in China［J］.Chinese Journal of Pathology,2021,50(04):323-332.
［15］沈勤.ALK阳性非小细胞肺癌的免疫组化染色筛查以及EML4-ALK融合亚型异质性的研究［D］.广州：南方医科大学,2017. SHEN Q.ALK associated NSCLC:Study and perspective of immunhistochemical screening and EML4-ALK fusion heterogeneity ［D］.Guangzhou:Southern Medical University,2017.
［16］SUN S,DU W,SUN Q,et al.Driver gene alterations profiling of Chinese non-small cell lung cancer and the effects of co-occurring alterations on immunotherapy［J］.Cancer Med,2021,10(20):7360-7372.
［17］朱丽蒙,马楠,任晓妮,等.基于1046例肺癌靶向基因检测的ARMS-PCR和NGS技术优势分析［J］.河南医学研究,2020,29(33):6152-6156. ZHU LM,MA N,REN XN,et al.Advantages of NGS and ARMS-PCR based on the detection of 1046 cases of lung cancer associated gene ［J］.Henan Medical Research,2020,29(33):6152-6156.
［18］周彩存,王洁,程颖,等.二代测序技术在NSCLC中的临床应用中国专家共识(2020版)［J］.中国肺癌杂志,2020,23(09):741-761. ZHOU CC,WANG J,CHENG Y,et al.Chinese Expert Consensus on next generation sequencing diagnosis for non-small cell lung cancer (2020 edition)［J］.Chin J Lung Cancer,2020,23(09):741-761.
［19］TSUNEZUKA Y,TANAKA N,FUJIMORI H,et al.The case of double primary lung adenocarcinomas with an EGFR mutation and ALK translocation successfully treated with alectinib at the post-surgical recurrence［J］.J Med Invest,2017,64(3.4):305-307.
［20］LI Y,SU S,CAI G,et al.Responses to crizotinib and chemotherapy in patients with lung adenocarcinoma harboring a concomitant EGFR mutation and ALK gene rearrangement:A case repot and review of the literature［J］.Mol Clin Oncol,2017,7(2):173-182.
［21］NGUYEN THT,PHAM XD,DAO KL,et al.Response to a combination of full-dose osimertinib and ceritinib in a non-small cell lung cancer patient with EML4-ALK rearrangement and epidermal growth factor receptor co-mutation［J］.Case Rep Oncol,2021,14(2):1085-1091.
［22］孙卓琛,田丰,魏俊.青年型肺腺癌临床特征及驱动基因突变的研究进展［J］.现代肿瘤医学,2024,32(07):1340-1343. SUN ZC,TIAN F,WEI J.Advances in clinical features and driver gene mutation of young patients with lung adenocarcinoma［J］.Modern Oncology,2024,32(07):1340-1343.
［23］洪子强,金大成,白向豆,等.多原发肺癌诊断与治疗的最新研究进展［J］.中国全科医学,2022,25(27):3435-3442. HONG ZQ,JIN DC,BAI XD,et al.Recent advances in the diagnosis and management of multiple primary lung cancer ［J］.Chinese General Practice,2022,25(27):3435-3442.
［24］FAN J,DAI X,WANG Z,et al.Concomitant EGFR mutation and EML4-ALK rearrangement in lung adenocarcinoma is more frequent in multifocal lesions［J］.Clin Lung Cancer,2019,20(4):e517-e530.

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