肺腺癌恶性胸腔积液中表皮生长因子受体鼠类肉瘤病毒癌基因 间变性淋巴瘤激酶基因突变与细胞亚型的相关性研究

Correlation between epidermal growth factor receptor,Kirsten rat sarcoma viral oncogene,anaplastic lymphoma kinase variants and cytological subtype in malignant pleural effusion of pulmonary adenocarcinoma

目的探讨肺腺癌恶性胸腔积液(MPE)中表皮生长因子受体(EGFR)、鼠类肉瘤病毒癌基因(KRAS)、间变性淋巴瘤激酶(ALK)基因突变状态与细胞学亚型的相关性。方法收集2017年10月至2020年10月确诊为肺腺癌MPE的细胞蜡块47例,依据肺腺癌国际多学科标准[国际肺癌研究协会/美国胸科学会/欧洲呼吸学会(IASLC/ATS/ERS)]对细胞学亚型进行分类;突变扩增系统(ARMS)法检测EGFR和KRAS基因突变,荧光原位杂交(FISH)法检测ALK基因重排,并结合临床特分析两者的相关性。结果47例肺腺癌MPE中EGFR突变率为51%(24/47),与女性患者、贴壁生长亚型和微乳头状亚型有关(P<0.05)。KRAS突变率为11%(5/47),与吸烟史有关(P<0.05)。ALK突变率为6%(3/47),与女性患者和黏液实体亚型有关(P<0.05)。结论EGFR、KRAS和ALK基因突变与临床特征存在一定的相关性,且EGFR在贴壁生长和微乳头状细胞学亚型中突变率更高,ALK突变在黏液实体状细胞学亚型中最常见。

Objective To investigate the correlation between epidermal growth factor receptor(EGFR),Kirsten rat sarcoma viral oncogene(KRAS),anaplastic lymphoma kinase(ALK)variants and cytological subtype in malignant pleural effusion(MPE)in patients with pulmonary adenocarcinoma.Methods Among 47 paraffin blocks with pulmonary adenocar-cinoma and MPE from October 2017 to October 2020 were enrolled.Cytological subtypes were classified according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society(IASLC/ATS/ERS)international multidisciplinary classification of pulmonary adenocarcinoma.EGFR and KRAS status were iden-tified by amplification refractory mutation system(ARMS)real-time polymerase chain reaction,ALK rearrangements were detected in a tissue microarray by using fluorescence in situ hybridization.Results The mutation rate of EGFR in pulmonary adenocarcinoma and MPE were 51%(24/47),which was related to female patients,lepidic growth subtypes,and micropapillary subtypes(P<0.05).The positive rate of KRAS mutation was 11%(5/47),which was related to smoking history(P<0.05).The detection rates of ALK were 6%(3/47),ALK gene mutation was mainly related to female and solid pattern with mucin secretion(P<0.05).Conclusion The positive of EGFR,KRAS and ALK mutation are correlated with clinicopathologic characteristics.The mutation rate of EGFR is relatively high in lepidic and micropapillary subtypes,and solid pattern with mucin secretion have a high mutation rate of ALK.