肺腺癌胸腔积液沉渣间变性淋巴瘤激酶融合基因蛋白表达与临床病理特征的关系及克唑替尼疗效观察
Relationship between expression of anaplastic lymphoma kinase in pleural effusion and clinicopathological features of patients with lung adenocarcinoma and the response to crizotinib
摘要目的 探讨原发性肺腺癌胸腔积液沉渣间变性淋巴瘤激酶(ALK)蛋白表达与临床病理特征的关系及克唑替尼的治疗效果.方法 回顾性分析2013年9月至2014年1 1月首都医科大学附属北京胸科医院以胸腔积液沉渣包埋标本进行ALK基因重排检测的原发性肺腺癌病例85例,男42例,女43例,年龄30~87岁,平均58岁.采用Ventana全自动免疫组织化学染色和D5F3抗体试剂盒检测ALK蛋白表达,分析表达阳性患者的临床病理特征及克唑替尼的疗效.结果 85例标本中ALK蛋白表达阳性13例(15.3%);<60岁患者ALK蛋白阳性12例,≥60岁1例(26.1%,2.6%,x2 =9.015,P=0.002);男性8例ALK蛋白表达阳性,女性5例(19.1%,11.6%,x2=0.903,P =0.259);不吸烟组ALK阳性8例,吸烟组5例(17.0%,13.5%,x2=0.379,P=0.827).13例ALK阳性患者中6例接受表皮生长因子受体(EGFR)基因突变检测,其中5例EGFR为野生型,1例不同肺叶病灶中检测出19外显子突变.13例ALK阳性患者中接受克唑替尼治疗4例,疗效评价均为部分缓解.结论 ALK蛋白阳性多见于晚期肺腺癌中较年轻的患者,ALK阳性患者罕见EGFR基因突变;对原发性肺腺癌合并胸膜转移出现恶性胸腔积液的患者,可根据胸腔积液沉渣包埋标本检测ALK蛋白表达,指导临床靶向治疗.
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abstractsObjective To explore the expression of anaplastic lymphoma kinase (ALK) protein in pleural effusion cells from patients with lung adenocarcinoma and to investigate the relationship between ALK status and the clinicopathological features,and the response to crizotinib.Methods Eighty-five cases were reviewed from Sept.2013-Nov.2014 at Beijing Chest Hospital.There were 42 males and 43 females,with a median age of 58 (30-87).ALK rearrangements were screened by using immunohistochemistry on Benchmark XT auto-stainer.Results The frequency of ALK positive reactivity was 15.3% among the 85 patients.The incidence of ALK expression was more frequent in patients < 60 years as compared with patients≥60 years of age(26.1%,2.6%,x2 =9.015,P =0.002).Among the ALK-positive patients,8 were males and 5 were females (19.1%,11.6%,x2 =0.903,P =0.259).There were 8 never-smokers and 5 smokers harboring ALK rearrangement(17.0%,13.5%,x2 =0.379,P =0.827).Among patients with ALK rearrangement,6 received EGFR detection,and 5 showed no EGFR mutation,and 1 showed 19del EGFR mutation.Among the 13 ALK-positive patients,4 received crizotinib therapy,and all showed partial response.Conclusion Patients with lung adenocarcinoma with ALK rearrangement were significantly younger than those with ALK wild-type,and ALK rearrangement was rarely concur with EGFR mutation.Screening ALK fusion protein expression in patients with lung adenocarcinoma by paraffin-embedded sediments of pleural effusion was useful in guide of crizotinib therapy.
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