【作者】 杨光；

【导师】 刘会宁； 柳立军；

【作者基本信息】 河北医科大学 ， 胸外科学， 2015， 硕士

【摘要】 目的:本研究采用电化学发光法和化学发光法对小细胞肺癌(small cell lung cancer,SCLC)相关肿瘤标志物(神经元特异性烯醇化酶(Neuron specific enolase,NSE)、癌胚抗原(Carcinoembryonic antigen,CEA)、鳞状上皮细胞癌抗原(Squamous cell carcinoma antigen,SCC))进行检测,分析血清中肿瘤标志物在EC化疗方案治疗前后的水平变化,并结合免疫组织化学法(immunohistochemistry)对病理组织进行分析,随访患者的生存状况,旨在探讨与SCLC相关的肿瘤标志物在SCLC的诊断、治疗效果评估及病理再分型中的价值,从而为临床应用提供指导。方法:1选取112例2008年1月—2014年1月河北省人民医院胸外科、肿瘤科确诊的SCLC患者,所有患者均采用EC化疗方案(卡铂,Carboplatin,CBP+依托泊苷,Etoposide,EPEG)治疗,于初次化疗前1周内及化疗后1周采集静脉血3ml,应用电化学发光法(electrochemiluminescence)和化学发光法对血清NSE、CEA、SCC的表达水平进行检测;同时选取同期河北省体检中心112例健康体检者作为对照组;2对2010年01月—2012年12月期间确诊的70例SCLC的病理组织标本进行重新切片,以免疫组织化学法检测突触素(synaptophysin,syn)、P63、甲状腺转录因子-1(thyroid transcription factor-1,TTF-1)的表达情况,从而区分出纯小细胞肺癌(pure small cell lung cancer,PSCLC)与复合性小细胞肺癌(combined small cell lung cancer,CSCLC)及可能误诊的非小细胞肺癌(non-small cell lung cancer,NSCLC);评估PSCLC患者与CSCLC患者在采取EC方案治疗一个周期后的治疗效果并进行生存分析;3统计学方法:所得数据应用SPSS 13.0统计软件进行统计学分析,计量数据结果的比较采用t检验,以(?x±s)表示,计数资料的比较采中,以P<0.05为差异有统计学意义。结果:1 NSE、CEA、SCC在SCLC患者血清中的表达水平本组小细胞肺癌患者血清中NSE、CEA、SCC水平与正常对照组相比均明显升高;三者的表达阳性率不同,NSE为79.46%(89/112),CEA为36.61%(41/112),SCC为9.82%(11/112),对三者阳性率进行组间比较,NSE的阳性率更高(P<0.05)。2不同分组的SCLC患者对EC方案的治疗敏感性根据SCLC患者NSE、CEA、SCC表达的不同情况分为单纯NSE升高组和其他组,单纯NSE升高组较其他组的治疗有效率更高,分别为69.44%和27.63%,经统计学检验,差异具有统计学意义(P<0.05)。3一期化疗有效者血清NSE、CEA、SCC的变化本组SCLC患者中,46例患者经一期化疗后效果明显,NSE在化疗后明显下降,结果有统计学差异(P<0.05),而CEA、SCC变化不明显(P>0.05)。4 Syn、TTF-1、P63在SCLC病理组织中的表达根据患者病理切片的免疫组织化学检测结果,本组病例中筛查出NSCLC 1例,并诊断为低分化鳞癌。另69例病理组织中syn阳性率97.10%(67/69)、P63阳性率11.59%(8/69)、TTF-1阳性率88.41%(61/69)。其中,PSCLC55例,SCLC复合鳞癌8例,SCLC复合腺癌6例。因此,将CSCLC病例归为一组,占本组病例的20.29%(14/69),将PSCLC病例归为另一组,占本组病例的79.71%(55/69)。5 NSE与SCLC病理分型的关系在69例SCLC患者中,单纯NSE升高者为一组,包括1例CSCLC,23例PSCLC;非单纯NSE升高者为另一组,包括13例CSCLC,32例PSCLC。经统计学分析,两组构成有明显差异,NSE与SCLC病理分型有明显相关关系。6 EC化疗方案对PSCLC和CSCLC的治疗效果第一次化疗结束后,PSCLC和CSCLC患者的治疗有效率分别为50.91%(28/55)、21.43%(3/14),PSCLC的治疗有效率明显高于CSCLC,差异有统计学意义(P<0.05)。7 PSCLC和CSCLC的生存分析在随访的69例小细胞肺癌患者中,总体OS为3~36个月,总体中位OS为18.3个月,比较两组病人的中位总生存时间OS,其中PSCLC的中位OS为19.9个月,CSCLC中位OS为12.0个月。经Kaplan-Meier检验,从生存曲线的结果可以显示出PSCLC的预后明显优于CSCLC,差异具有统计学意义(P<0.05)。结论:1 NSE对SCLC的预测价值更大,可以作为监测SCLC治疗效果的敏感指标;2 NSE、CEA、SCC的联合应用对SCLC化疗方案的选择具有指导意义;3 NSE与SCLC病理分型相关,对于血清肿瘤标志物检测结果中非单纯NSE升高者,有必要行病理再分型分析;4联合免疫组织化学法检测syn、P63、TTF-1可更准确的分析小细胞肺癌的病理情况;5 EC化疗方案对PSCLC的治疗效果优于CSCLC。更多还原

【Abstract】 Objective:In this study, tumor markers(Neuron specific enolase, NSE 、Carcinoembryonic antigen, CEA、Squamous cell carcinoma antigen, SCC) related with small cell lung cancer(SCLC) were detected by electrochemiluminescence and chemiluminescent. The changes of the levels of tumor markers in serum were analyzed before and after chemotherapy of EC scheme. And the pathological tissue of SCLC was analysed by immunohistochemistry. Survival condition of patients with SCLC was followed up. The purpose is to discuss the value of tumor markers related with SCLC in the diagnosis,evaluation of treatment effect and pathological subtype in SCLC. Then it can be provided to the guidance for clinical application.Methods:1 112 patients with SCLC were selected from Thoracic Department and Oncology Department in Hebei General Hospital during January 2008 to January 2014. All patients were treated by the EC scheme(Carboplatin+Etoposide). The 3ml blood was obtained 1week before the first chemotherapy and 1 week after the chemotherapy. The levels of serum NSE、CEA and SCC were assayed by electrochemiluminescence and chemiluminescent. At the same time, 112 healthy subjects from Hebei Medical Examination Cencer were sclected as the control group.2 70 cases of pathological tissue specimens diagnosed during January 2010 to December 2012 were resectioned. Immunohistochemistry was used to detect the expressions of synaptophysin(syn), P63 and thyroid transcription factor-1(TTF-1). Then the pathological sections were retyped to distinguish the pure small cell lung cancer(PSCLC), combined small cell lung cancer(CSCLC) and the non-small cell lung cancer(NSCLC)misdiagnosed possibly. Treatment effects after the first chemotherapy of EC scheme between PSCLC and CSCLC were evaluated. They were followed up and survival analysis was performed among them.3 Statistical Methods: All data were analyzed by the SPSS 13.0 statistical software. Measurement data were compared by the test of t, and they were described by -x ±s.Well, the count data were compared by the test of χ2. Survival time of objects was analyzed by the curves of Kaplan-Meier. Among them, P value <0.05 was statistically significant.Results:1 The expression levels of NSE, CEA and SCC in the serum of patients with SCLCCompared to the control group, the levels of NSE, CEA and SCC in serum in the group of patients with SCLC were significantly increased. Among them, the positive rates were different. The positive rate of NSE was 79.46%(89/112). While CEA was 36.61%(41/112) and SCC was 9.82%(11/112). The positive rates of the three groups were compared between each other. The positive rate of NSE standed for the highest(P<0.05).2 Treatment sensitivity to EC scheme among different groupsAccording to the different expression of NSE, CEA and SCC, patients with SCLC can be divided into the NSE simply elevated group and the other group. Compared with the other group, the NSE simply elevated group had higher efficiency, respectively 69.44% and 27.63%. The results were analyzed by statistical test. The difference was statistically significant(P<0.05).3 Changes of the levels of NSE、CEA and SCC in serum of effective patients with SCLC after a course of chemotherapyIn the patients with SCLC that were studied, the effect in 46 patients after a course of chemotherapy was obvious. The level of NSE decreased significantly after the therapy and this result had significant difference(P<0.05). While the levels in CEA and SCC did not change significantly(P>0.05).4 The expression of syn、TTF-1、P63 in pathological tissues of SCLCAccording to the immunohistochemical detecting results in pathological sections, 1 cases of NSCLC was tested in this group of cases, which was diagnosed as poorly differentiated squamous cell carcinoma. In the other 69 pathological cases, the positive rate of syn was 97.1%(67/69).While the P63 was 11.6%(8/69) and TTF-1 was 88.4%(61/69). The group of 69 cases contained 55 cases of PSCLC, 8 cases of SCLC composite squamous cell carcinoma and 6 cases of SCLC composite adenocarcinoma. The group including all cases of CSCLC accounted for 20.29%(14/69). PSCLC was another group, which accounted for 79.71%(55/69).5 The relationship of NSE and pathology typing of SCLCAmong the 69 patients with SCLC, the NSE simply elevated group as one group included 1 case of CSCLC and 23 cases of PSCLC. The NSE not simply elevated group was the other one, including 13 cases of CSCLC and 32 cases of PSCLC. Analyzed by statistics, the difference of constitute between the two groups was statistically significant.There was significant relationship between NSE and pathology typing of SCLC.6 Treatment effect of chemotherapy of EC scheme to PSCLC and CSCLCAfter the first course of chemotherapy, the effective treatment rates between PSCLC and CSCLC were 60%(33/55) and 14.28%(2/14). The effective treatment rate of PSCLC was significant higher than the CSCLC. The difference was statistically significant(P<0.05).7 Survival analysis between PSCLC and CSCLCAmong the 69 SCLC patients followed up, the whole OS was between 3~ 36 months. The whole median OS was 18.3 months. The median OS of PSCLC was 19.9 months and that of CSCLC was 12 months. After tested by Kaplan-Meier, the survival curve showed the prognosis of PSCLC was better than that of CSCLC. That result tested by statistical method has significant difference(P<0.05).Conclusion:1 NSE is more valuable to predict SCLC. It can be a sensitive indicator to monitor the therapeutic effect of SCLC.2 The union detection of NSE、CEA and SCC has guiding significance to choose the scheme of chemotherapy.3 There is significant relationship between NSE and pathology typing of SCLC. It is necessary to analyse the pathological subdivided type in patients with NSE not simply elevated in serum tumor markers detection.4 The pathological type of SCLC can be more accurately analysed by the union detection of syn 、 P63 and TTF-1 through immunohistochemi-cal method.5 The effect of EC scheme in PSCLC is significantly better than that in CSCLC.更多还原