發(fā)布時間：2018-03-21 12:27

  本文選題：肺腫瘤　切入點：非小細胞肺癌　出處：《安徽醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的棘皮動物微管相關蛋白 4 (echinoderm microtubule-associated protein-like4,EML4)與間變性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因是非小細胞肺癌(Non-small-cell lung cancer, NSCLC)患者常見驅(qū)動基因之一,本研究旨在探討EML4-ALK融合基因陽性患者(EML4-ALK+NSCLC)的檢測、臨床特征、治療、預后以及與EGFR、KRAS、BRAF基因表達情況之間的聯(lián)系。方法選取在我院診斷和住院治療的NSCLC患者190例作為研究對象,采用免疫組化(immunohistochemistry,IHC)法進行EML4-ALK+NSCLC篩選,對于IHC陽性的患者使用熒光定量PCR (RT-PCR)法驗證。收集整理EML4-ALK+NSCLC患者的臨床診斷、腫瘤分期、治療資料,并對其隨訪。對所有患者標本同時采用RT-PCR法進行多基因(EGFR、KRAS、BRAF突變)聯(lián)合檢測。結(jié)果190例NSCLC患者中,經(jīng)IHC篩查及RT-PCR確證,共檢出17例EML4-ALK+NSCLC,陽性率為8.95%。其中手術標本最多(47.1%, 8/17)(x2=25.999, P=0.000),EMIL4-ALK+NSCLC特征為年齡小于60歲的患者多見(占76.47%,13/17)(x2=5.813, P=0.016)。女性患者占70.59% (12/17),無吸煙史的患者占76.47%(13/17),病理類型以浸潤性腺癌實體為主型占58.82% (10/17),但均未發(fā)現(xiàn)有統(tǒng)計學差異。未發(fā)現(xiàn)同時出現(xiàn)EML4--ALK融合基因及EGFR、KRAS、BRAF突變的患者。在手術Ⅰ期患者中未發(fā)現(xiàn)EML4-ALK+NSCLC,在Ⅱ-Ⅲa期檢出8例EML4-ALK+NSCLC,經(jīng)術后化療25% (2/8)復發(fā),2年生存達到100%。9例晚期EML4-ALK+NSCLC化療有效率低(4療程化療后僅12.5%緩解),5例患者已經(jīng)死亡。一線化療后病情穩(wěn)定或緩解患者一線維持階段口服克唑替尼療效滿意,均達到較長期緩解,目前生存良好。多線治療后進展患者三線服用ALK-TKI仍然帶來病情緩解,但獲益有限。結(jié)論通過IHC篩查及隨后RT-PCR可在手術標本、淋巴結(jié)活檢標本、支氣管鏡活檢標本、肺穿刺及胸水沉渣包埋標本有效檢出EML4-ALK+NSCLC。EML4-ALK+NSCLC臨床特征為小于60歲的患者多見,腫瘤晚期及浸潤性肺腺癌實體型多見,而與吸煙史無明顯關聯(lián)。能夠手術的較早期EML4-ALK+NSCLC(Ⅱ-Ⅲa期),手術加上術后輔助化療預后較好;晚期患者一線化療后病情穩(wěn)定或緩解患者口服EML4-ALK-TKI——克唑替尼療效很好,經(jīng)多線治療后服用克唑替尼仍然可提高EML4-ALK+NSCLC的緩解率。
[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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