Article Abstract

A study of EGFR wild-type non-small cell lung cancer ALK genetic mutation

Authors: Shoufeng Wang, Naiquan Mao, Chuantian Zuo, Hong Pan, Tong Xie, Yaoyuan Huang, Qi Pan, Junwei Wu

Abstract

Background: the positive rate and clinicopathological features of EML4-ALK, the relationship between EGFR mutations in non-small cell lung cancer (NSCLC) patients are the state of confusion, automatic immunohistochemistry to detect the expression of ALK protein, to provide reference for clinical diagnosis and treatment.
Methods: From October 2011 to December 2014, 300 NSCLC archived samples in Guangxi medical university affiliated tumor hospital pathology department were selected. The EGFR genetic mutation of 300 lung cancer samples were detected by amplification refractory mutation system (ARMS) (Qiagen Inc., Valencia, CA, USA). The detection results were divided into EGFR mutant type and wild type group, and the protein expression of EML4-ALK fusion gene was detected by immunohistochemistry (IHC), (Ventana kit, Ventana Medical Systems, Inc., Mountain View, CA, USA). Statistical methods (enumeration data were tested by chi-square test and Fisher’s exact test) were performed to compare the results between groups, and correlation analysis was performed by Spearman test.
Results: (I) The mean age of 300 NSCLC patients was 58.47 years, 156 patients were younger than 60 years, and 144 patients were older than 60 years. Gender: 178 patients were male, 59.33%; 122 patients were female, 40.67%. Smoking history: 186 patients had no smoking history, 62.00%; 114 patients had smoking history, 38.00%. Pathological type: adenocarcinoma 239 cases, 79.67%; squamous carcinoma 36 cases, 12.00%; adenosquamous carcinoma 10 cases, 3.33%; neuroendocrine carcinoma 2 cases, 0.67%; carcinoid 1 case, 0.33%; sarcomatoid carcinoma 3 cases, 1.00%; lymphoepithelial carcinoma 1 case, 0.33%; bronchiolo-alveolar carcinoma 1 case, 0.33%; the other 6 cases, 2.00%. Clinical stages: stage IV 69 cases, stage III 91 cases, stage II 46 cases, and stage I 94 cases. (II) Among 300 NSCLC samples, 130 cases were detected EGFR genetic mutation, the mutant rate was 43.33%, among which 58 cases were 21 exon L858R mutation (44.62%), 1 case was 21 exon L861Q mutation (0.77%), 69 cases were 19 exon mutation (53.08%), 1 case was 19del + 20T790MR amphimutation and 1 case was 20T790M + L858R amphimutation. (III) Among 300 NSCLC samples, 13 cases EML4-ALK expression were positive. The difference of age, gender, smoking history, pathological stage, tissue differentiation and lymph node metastasis had no statistical significance between EML4-ALK fusion gene positive and negative patients. (IV) The clinical feature constituent ratio of 13 cases EML4-ALK fusion gene positive patients indicated that the positive cases were more common in young (76.92%), non-smoking (84.62%), male (69.23%), and adenocarcinoma (100.00%) patients. (V) Among 13 EML4-ALK fusion gene positive patients, 1 case’s EGFR was mutant type, 12 cases’ were wild-type. The correlation analysis of EML4-ALK and EGFR in NSCLC patients indicated that they were negative correlated, and the difference had statistical significance (R=−0.153, P=0.008).
Conclusions: (I) Using fully automatic immunohistochemistry (Ventana) to detect ALK gene was a method easy and simple to handle, cheap, standard, easy to interpret and could be good quality control. This method was suitable for clinical application. (II) EML4-ALK fusion gene was a new NSCLC molecular subtype after EGFR. ALK gene positive cases were more common in young, nonsmoking and adenocarcinoma patients, this could provide certain reference for clinical screening potential benefit population of EML4-ALK mutation. (III) ALK gene rearrangement was negative correlated with EGFR; and ALK rearrangement could coexist with EGFR mutation.

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