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  本文選題：肺腺癌 + TTF-1�。� 參考：《皖南醫(yī)學院》2017年碩士論文

【摘要】：目的:目前,關(guān)于肺腺癌患者分子靶向治療獲益的關(guān)鍵是治療前行EGFR基因檢測,了解基因突變狀況,但該過程繁瑣、費用高及假陰性等使部分患者失去了檢測時機,延誤治療。因此,有必要探尋新的與EGFR基因突變有關(guān)的標志物預測其突變來指導臨床治療。甲狀腺轉(zhuǎn)錄因子-1(TTF-1)與天門冬氨酸蛋白酶A(Napsin A)作為肺腺癌患者的診斷標志物,一般采用免疫組化法測定,此方法比EGFR基因突變檢測更為簡便、快速。據(jù)此,本項實驗采用免疫組化法檢測肺腺癌中TTF-1與Napsin A的表達和ARMS法檢測EGFR突變,探討肺腺癌組織中二者的表達情況與EGFR突變狀態(tài)的相關(guān)性及臨床預測價值。方法:收集2014年03月至2016年06月在皖南醫(yī)學院弋磯山醫(yī)院病理科經(jīng)組織學確診的原發(fā)性肺腺癌患者160例,入選的所有患者均行EGFR突變檢測,并有完整的檢測結(jié)果。所有病例取材前均未接受放療和化療,并且能獲得較為完整的臨床資料。所有相關(guān)資料均從患者既往住院病歷庫中調(diào)閱,包括年齡、性別、吸煙史、組織分化程度、TNM分期。所有標本均經(jīng)10%中性緩沖甲醛固定,石蠟包埋,HE染色后在光鏡下觀察形態(tài)學改變,應用免疫組化法檢測TTF-1和Napsin A的表達情況,應用ARMS法檢測患者EGFR的突變狀況。采用SPSS18.0軟件分析系統(tǒng),計數(shù)資料用χ2檢驗,P0.05為差異有統(tǒng)計學意義。結(jié)果:1.入組肺腺癌患者中EGFR突變率為55%,主要發(fā)生在19和21外顯子,19外顯子占52.3%,21外顯子占43.1%。女性(P=0.001)、不吸煙(P=0.026)、組織分化程度較高(P=0.021)的患者具有更高的EGFR突變;2.TTF-1和Napsin A在肺腺癌中的陽性表達率分別為88.1%和86.3%,兩者雙陽性表達率為83.1%,且二者的表達與年齡、TNM分期沒有相關(guān)性(P0.05),而與性別(P=0.012、P=0.035)、吸煙(P=0.018、P=0.036)、組織分化程度(P=0.013、P=0.009)密切相關(guān)。二者具有很好的正相關(guān)性(Kappa系數(shù)=0.637,r=0.639,P=0.000),TTF-1和Napsin A在女性、不吸煙、組織分化程度較高的肺腺癌患者中表達率較高;3.TTF-1和Napsin A表達與EGFR突變明顯正相關(guān)(r=0.367、P=0.000,r=0.405、P=0.000),TTF-1陽性與陰性表達中EGFR突變率分別為61.7%、5.3%,差異具有統(tǒng)計學意義(P=0.000),TTF-1預測EGFR突變的靈敏度為98.9%,特異度為25%,陽性預測價值為61.7%,陰性預測價值為94.7%;Napsin A陽性與陰性表達中EGFR突變率分別為63%、4.5%,差異具有統(tǒng)計學意義(P=0.000),Napsin A預測EGFR突變的靈敏度為98.9%,特異度為29.2%,陽性預測價值為63.0%,陰性預測價值為95.5%;兩者雙陽性表達的EGFR突變率為65.4%,二者聯(lián)合預測EGFR突變的靈敏度為98.9%,特異度為36.1%,陽性預測價值為65.4%,陰性預測價值為96.3%。結(jié)論:1.在肺腺癌中EGFR突變狀態(tài)較高,多見于19、21外顯子,女性、不吸煙、組織分化較高可以預測肺腺癌患者的高EGFR突變率;2.TTF-1和Napsin A在肺腺癌組織中的表達水平較高,二者顯著相關(guān),可作為肺腺癌診斷的參考指標,特別是在女性、不吸煙、組織分化程度較高的肺腺癌患者中表達明顯;3.肺腺癌組織中TTF-1和Napsin A表達與EGFR突變具有很好的相關(guān)性,二者的表達水平可以預測EGFR突變狀態(tài),且TTF-1與Napsin A聯(lián)合表達具有更高的EGFR突變可能,為臨床肺腺癌患者靶向治療提供參考價值。
[Abstract]:Objective: at present, the key to the molecular targeting therapy of lung adenocarcinoma is to treat the EGFR gene and understand the mutation of the gene, but the process is tedious, the high cost and the false negative cause some patients to lose the time of detection and delay the treatment. Therefore, it is necessary to explore new markers related to the mutation of EGFR gene to predict their mutation To guide clinical treatment, thyroid transcription factor -1 (TTF-1) and aspartic proteinase A (Napsin A) are used as diagnostic markers for lung adenocarcinoma, and are generally determined by immunohistochemical method. This method is more convenient and rapid than EGFR gene mutation detection. Accordingly, this experiment uses immunohistochemical method to detect TTF-1 and Napsin A in lung adenocarcinoma. The correlation of the expression of two in the lung adenocarcinoma tissue and the mutation status of EGFR in the lung adenocarcinoma tissue and the clinical predictive value were examined by ARMS method. Methods: 160 cases of primary lung adenocarcinoma confirmed by histology of the pathology department of Yi La hospital from 03 months to 06 months of 2016 were collected from 03 months to 06 months of 2014. All the patients were selected for EGFR mutation. All cases were not treated with radiotherapy and chemotherapy before all cases were taken, and more complete clinical data were obtained. All the related data were read from the patient's Hospital history library, including age, sex, smoking history, degree of tissue differentiation, TNM staging. All specimens were fixed by 10% neutral buffered formaldehyde and paraffin wax. After HE staining, the morphological changes were observed under the light microscope. The expression of TTF-1 and Napsin A was detected by immunohistochemistry. The mutation of EGFR was detected by ARMS. The SPSS18.0 software was used to analyze the system. The count data was tested by chi 2, and P0.05 was statistically significant. The result: the EGFR mutation rate in the 1. patients with lung adenocarcinoma was 55%. Mainly in exons 19 and 21, 19 exons 52.3%, 21 exons in 43.1%. women (P=0.001), non smoking (P=0.026), and higher tissue differentiation (P=0.021) patients with higher EGFR mutations; the positive expression rate of 2.TTF-1 and Napsin A in lung adenocarcinoma was 88.1% and 86.3%, both positive expression rates were 83.1%, and the two person's table TNM staging was not associated with age (P0.05), but was closely related to sex (P=0.012, P=0.035), smoking (P=0.018, P=0.036), and the degree of tissue differentiation (P=0.013, P=0.009). The two had a good positive correlation (Kappa coefficient =0.637, r=0.639, P=0.000). The expression of 3.TTF-1 and Napsin A was positively correlated with EGFR mutation (r=0.367, P=0.000, r=0.405, P=0.000). The EGFR mutation rate of TTF-1 positive and negative expression was 61.7%, 5.3%, respectively, and the difference was statistically significant (P=0.000). The sensitivity of the TTF-1 prediction mutation was 98.9%, the specificity was 25%, the positive predictive value was 61.7%, negative predictive value was predicted. The value was 94.7%; the EGFR mutation rate in the positive and negative expression of Napsin A was 63%, 4.5%, and the difference was statistically significant (P=0.000). The sensitivity of EGFR mutation was 98.9%, the specificity was 29.2%, the positive predictive value was 63%, the negative predictive value was 95.5%, the EGFR mutation rate of the double positive expression of two was 65.4%, and two predicted EGF. The sensitivity of the R mutation was 98.9%, the specificity was 36.1%, the positive predictive value was 65.4%, the negative predictive value was 96.3%. conclusion: 1. in the lung adenocarcinoma, the EGFR mutation was higher, more seen in exon 19,21, women, non smoking, high tissue differentiation can predict the high EGFR mutation rate of lung adenocarcinoma patients; 2.TTF-1 and Napsin A in the lung adenocarcinoma tissue High level, two significant correlation, can be used as a reference index for diagnosis of lung adenocarcinoma, especially in women, non smoking, highly differentiated lung adenocarcinoma patients, 3. lung adenocarcinoma tissue TTF-1 and Napsin A expression and EGFR mutation has a good correlation, the level of expression of the two can predict EGFR mutation state, and TTF- 1 the combined expression of Napsin and A may have a higher EGFR mutation, which can provide a reference value for targeted therapy in clinical lung adenocarcinoma patients.
【學位授予單位】：皖南醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2

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