非小细胞肺癌患者EML4-ALK基因检测及EML4-ALK阳性患者临床特征分析

发布时间：2018-03-21 12:27

  本文选题：肺肿瘤　切入点：非小细胞肺癌　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的棘皮动物微管相关蛋白 4 (echinoderm microtubule-associated protein-like4,EML4)与间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因是非小细胞肺癌(Non-small-cell lung cancer, NSCLC)患者常见驱动基因之一,本研究旨在探讨EML4-ALK融合基因阳性患者(EML4-ALK+NSCLC)的检测、临床特征、治疗、预后以及与EGFR、KRAS、BRAF基因表达情况之间的联系。方法选取在我院诊断和住院治疗的NSCLC患者190例作为研究对象,采用免疫组化(immunohistochemistry,IHC)法进行EML4-ALK+NSCLC筛选,对于IHC阳性的患者使用荧光定量PCR (RT-PCR)法验证。收集整理EML4-ALK+NSCLC患者的临床诊断、肿瘤分期、治疗资料,并对其随访。对所有患者标本同时采用RT-PCR法进行多基因(EGFR、KRAS、BRAF突变)联合检测。结果190例NSCLC患者中,经IHC筛查及RT-PCR确证,共检出17例EML4-ALK+NSCLC,阳性率为8.95%。其中手术标本最多(47.1%, 8/17)(x2=25.999, P=0.000),EMIL4-ALK+NSCLC特征为年龄小于60岁的患者多见(占76.47%,13/17)(x2=5.813, P=0.016)。女性患者占70.59% (12/17),无吸烟史的患者占76.47%(13/17),病理类型以浸润性腺癌实体为主型占58.82% (10/17),但均未发现有统计学差异。未发现同时出现EML4--ALK融合基因及EGFR、KRAS、BRAF突变的患者。在手术Ⅰ期患者中未发现EML4-ALK+NSCLC,在Ⅱ-Ⅲa期检出8例EML4-ALK+NSCLC,经术后化疗25% (2/8)复发,2年生存达到100%。9例晚期EML4-ALK+NSCLC化疗有效率低(4疗程化疗后仅12.5%缓解),5例患者已经死亡。一线化疗后病情稳定或缓解患者一线维持阶段口服克唑替尼疗效满意,均达到较长期缓解,目前生存良好。多线治疗后进展患者三线服用ALK-TKI仍然带来病情缓解,但获益有限。结论通过IHC筛查及随后RT-PCR可在手术标本、淋巴结活检标本、支气管镜活检标本、肺穿刺及胸水沉渣包埋标本有效检出EML4-ALK+NSCLC。EML4-ALK+NSCLC临床特征为小于60岁的患者多见,肿瘤晚期及浸润性肺腺癌实体型多见,而与吸烟史无明显关联。能够手术的较早期EML4-ALK+NSCLC(Ⅱ-Ⅲa期),手术加上术后辅助化疗预后较好;晚期患者一线化疗后病情稳定或缓解患者口服EML4-ALK-TKI——克唑替尼疗效很好,经多线治疗后服用克唑替尼仍然可提高EML4-ALK+NSCLC的缓解率。
[Abstract]:Objective to investigate the detection of EML4-ALK in non-small cell lung cancer (NSCL) patients with non-small cell lung cancer (NSCL), a fusion gene of acanthoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinases (ALK4). Methods 190 patients with NSCLC diagnosed and hospitalized in our hospital were selected as study subjects, and were screened for EML4-ALK NSCLC by immunohistochemical histochemistry-IHC method. IHC positive patients were verified by fluorescence quantitative PCR RT-PCR method. The clinical diagnosis, tumor staging and treatment data of EML4-ALK NSCLC patients were collected and sorted out. At the same time, all the samples were detected by RT-PCR method. Results among the 190 patients with NSCLC, they were screened by IHC and confirmed by RT-PCR. A total of 17 cases of EML4-ALK were detected, and the positive rate was 8.955.The most of them were surgical specimens (47.1%), and 8 / 17% of them (25.999). The characteristics of EMIL4-ALK NSCLC were more common in patients younger than 60 years of age (76.477.47% 13 / 17% x 25.813, P 0.01616%). Female patients accounted for 70.59% / 1217%, and those with no history of smoking accounted for 76.4717% of the total. The pathological types were infiltrating solid carcinoma of the gonad gland in 76.4717% (76.4717%). The dominant type accounted for 58.82% / 10 / 17 / 17, but no statistical difference was found. No EML4--ALK fusion gene and EGFR KRASA BRAF mutation were found at the same time. No EML4-ALK NSCLC was found in the patients with stage 鈪，

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