本文選題：肺腫瘤　切入點(diǎn)：非小細(xì)胞肺癌　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的棘皮動(dòng)物微管相關(guān)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(xì)胞肺癌(Non-small-cell lung cancer, NSCLC)患者常見(jiàn)驅(qū)動(dòng)基因之一,本研究旨在探討EML4-ALK融合基因陽(yáng)性患者(EML4-ALK+NSCLC)的檢測(cè)、臨床特征、治療、預(yù)后以及與EGFR、KRAS、BRAF基因表達(dá)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(duì)象,采用免疫組化(immunohistochemistry,IHC)法進(jìn)行EML4-ALK+NSCLC篩選,對(duì)于IHC陽(yáng)性的患者使用熒光定量PCR (RT-PCR)法驗(yàn)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(duì)其隨訪。對(duì)所有患者標(biāo)本同時(shí)采用RT-PCR法進(jìn)行多基因(EGFR、KRAS、BRAF突變)聯(lián)合檢測(cè)。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(yáng)性率為8.95%。其中手術(shù)標(biāo)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(jiàn)(占76.47%,13/17)(x2=5.813, P=0.016)。女性患者占70.59% (12/17),無(wú)吸煙史的患者占76.47%(13/17),病理類(lèi)型以浸潤(rùn)性腺癌實(shí)體為主型占58.82% (10/17),但均未發(fā)現(xiàn)有統(tǒng)計(jì)學(xué)差異。未發(fā)現(xiàn)同時(shí)出現(xiàn)EML4--ALK融合基因及EGFR、KRAS、BRAF突變的患者。在手術(shù)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(shù)后化療25% (2/8)復(fù)發(fā),2年生存達(dá)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(mǎn)意,均達(dá)到較長(zhǎng)期緩解,目前生存良好。多線治療后進(jìn)展患者三線服用ALK-TKI仍然帶來(lái)病情緩解,但獲益有限。結(jié)論通過(guò)IHC篩查及隨后RT-PCR可在手術(shù)標(biāo)本、淋巴結(jié)活檢標(biāo)本、支氣管鏡活檢標(biāo)本、肺穿刺及胸水沉渣包埋標(biāo)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(jiàn),腫瘤晚期及浸潤(rùn)性肺腺癌實(shí)體型多見(jiàn),而與吸煙史無(wú)明顯關(guān)聯(lián)。能夠手術(shù)的較早期EML4-ALK+NSCLC(Ⅱ-Ⅲa期),手術(shù)加上術(shù)后輔助化療預(yù)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，

本文編號(hào)：1643849