DNA倍体联合肿瘤标志物检测在胸腔积液诊断中的应用

目的探讨DNA倍体分析联合肿瘤标志物在良、恶性胸腔积液诊断中的价值。方法将108例胸腔积液分为恶性组（68例）和良性组（40例）。除常规细胞学检查外,以流式细胞术（flowcytometry,FCM）检测患者胸腔积液中的DNA倍体,采用化学发光法测定胸腔积液中CEA、CA199、NSE、CYFRA211、SCC、CA125等肿瘤标志物含量。比较DNA倍体联合肿瘤标志物诊断与细胞学诊断的优劣。结果DNA倍体诊断恶性胸腔积液的敏感性、特异性分别为70．6％、95．0％,Youden’s指数为0．656,敏感度稍高于细胞学诊断的65．1％,差异无统计学意义（P〉0．05）。除NSE外,其他5种肿瘤标志物在恶性胸腔积液中浓度均高于良性,差异有统计学意义（P〈0．05）。CYFRA211、CEA、CAl99、CAl25、SCC、NSE的AUC分别为：0．893,0．828,0．759,0．691,0．524及0．490;COV分别为：149．2ng／mL,53．6ng／mL,78．2IU／mL,1559．0IU／mL,48．72ng／mL及78．3ng／mL;敏感性分别为：44．1％,44．1％,35．3％,29．4％,13．2％,5．9％,特异性均为100％。4种肿瘤标志物联合检测＋DNA倍体检测的敏感性为88．2％（60／68）,特异性95％,显著高于细胞学诊断。结论DNA倍体联合CEA、CA199、CYFRA211和CA125检测诊断恶性胸腔积液有较高敏感性,具有定量、快速、价廉、易标准化的特点,且操作简单。     

胸水CA125、CA199、CEA、NSE、CYFRA21-1、CA72-4对原发性肺癌的诊断价值

目的探讨胸水中糖链抗原125（CA125）、糖链抗原199（CA199）、癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19片段（CYFRA21—1）和糖链抗原72-4（CA72-4）在原发性肺癌并胸腔积液的诊断和鉴别诊断、病理分型中的价值。方法采用电化学免疫荧光发光法同时检测90例原发性肺癌并胸腔积液患者（恶性胸腔积液组）和64例良性胸腔积液患者（良性胸腔积液组）胸水中CA125、CA199、CEA、NSE、CYFRA21-1和CA72-4水平。结果恶性胸腔积液组各胸水肿瘤标志物水平均高于良性胸腔积液组（P〈0．05）,其中CEA、CYFRA21-1、NSE分别对腺癌、鳞癌、小细胞肺癌最敏感。联合检测以CEA＋NSE＋CYFRA21-1最优,可使敏感性达98．9％,阴性预测值至96．6％,准确性提高至76．0％。结论胸水肿瘤标志物在原发性肺癌的诊断中价值较高,其中CEA的诊断价值最大,联合检测诊断准确性优于单项检测。     

肿瘤分子标志联合检测对胸腔积液鉴别诊断价值分析

目的:探讨癌胚抗原(CEA)、糖类抗原125(CA125)、细胞角蛋白片段19(CYFRA21-1)和神经元特异性烯醇化酶(NSE)联合检测在良恶性胸腔积液鉴别诊断中的价值。方法:电化学发光法检测56例恶性胸腔积液患者和78例良性胸腔积液患者的CEA、CA125、CYFRA21-1和NSE的浓度和阳性表达率,比较其差异。结果:恶性组与良性组CEA(t=5.102)、CA125(t=4.294)、CYFRA21-1(t=3.602)和NSE(t=2.142)浓度进行比较,差异均有统计学意义,P值均<0.05。恶性组与良性组CEA(χ2=69.07)、CA125(χ2=67.34)、CYFRA21-1(χ2=73.99)和NSE(χ2=78.59)阳性率进行比较,差异有统计学意义,P值均<0.01。单项检测各种肿瘤分子标志诊断良恶性胸腔积液的敏感度和特异性以CEA最高,分别为33.93%(19/56)和97.44%(76/78)。联合检测较单项检测敏感度明显增高。2项检测以CEA和CYFRA21-1敏感性和特异性最高,分别为44.64%(25/56)和96.15%(75/78)。3项检测以CEA、CYFRA21-1和NSE联合检测敏感性和特异性最高,分别为51.79%(29/56)和91.03%(71/78)。CEA+CA125+CYFRA21-1+NSE 4项联合检测效果最佳,其敏感性高达53.57%(30/56),特异度达85.90%(67/78)。结论:胸腔积液CEA、CA125、CYFRA21-1和NSE联合检测在良恶性胸腔积液鉴别诊断中有重要意义。     

肿瘤标志物对癌性胸腔积液诊断的价值

目的探讨肿瘤标志物在癌性胸腔积液诊断中的价值。方法应用免疫放射分析法对108例癌性胸腔积液和90例良性胸腔积液的CYFRA21-1、CEA、NSE和CA153含量进行检测,并对结果进行比较分析。结果癌性胸腔积液中四种肿瘤标志物指标明显高于良性组(P<0.01),四项联检后的敏感性、特异性及准确性明显升高。结论肿瘤标志物CYFRA21-1、CEA、NSE和CA153四项联检在癌性胸腔积液的诊断中具有明确的意义。     

检测肿瘤标志物ProGRP、NSE、CYFRA21-1、CEA对胸腔积液鉴别诊断价值的研究

背景与目的 恶性胸腔积液多由肺癌引起，肿瘤标志物检测对其鉴别诊断有一定临床价值。本研究的目的是探讨血清及胸腔积液胃泌素前体释放肽片断31—98（ProGRP）、神经元烯醇化酶（NSE）、细胞角蛋白19（cYFRA21—1）和癌胚抗原（CEA）单项或联合检测对肺癌所致恶性胸腔积液鉴别诊断与组织学分型的临床价值。方法 将肺癌所致的恶性胸腔积液患者按原发肿瘤类型分为小细胞肺癌（SCLC）组、肺腺癌组及肺鳞癌组，同时以良性胸腔积液组、健康对照组作为对照。评估胸腔积液ProGRP、NSE、CYFRA21—1和CEA单项及联合检测对各组恶性胸腔积液的诊断价值。结果 血清及胸腔积液ProGRP、NSE、CYFRA21—1、CEA在各恶性胸腔积液组的水平均明显高于对照组（P〈0．01）。SCLC组检测胸腔积液ProGRP的Youden指数和诊断准确性最高；肺腺癌和肺鳞癌组则以胸腔积液CEA＋CYFRA21—1联合检测（按平行试验）的Youden指数及诊断准确性最高。结论胸腔积液肿瘤标志物系列（ProGRP、NSE、CYFRA21—1、CEA）检查对恶性胸腔积液的鉴别诊断与组织学分型有很大的临床价值。胸腔积液ProGRP为SCLC所致恶性胸腔积液的最佳肿瘤标志物；胸腔积液cEA＋cYFRA21—1联合检测（按平行试验）为肺腺癌、肺鳞癌所致恶性胸腔积液较好的辅助诊断指标。     

CEA、CA199和细胞形态学联合检测对281例良、恶性胸腔积液鉴别诊断的临床意义

[目的]探讨肿瘤标志物CEA、CA199、细胞形态学联合检测在鉴别良、恶性胸腔积液中的临床意义。[方法]收集281例胸腔积液患者,其中恶性组149例,良性组132例。采用化学发光免疫法测定患者血清及胸腔积液中CEA和CA199水平。胸腔积液经离心、推片和瑞氏染色后进行细胞形态学检查,以鉴别胸腔积液的良、恶性,并评价CEA、CA199、细胞形态学联合检测在鉴别良、恶性胸腔积液诊断中的敏感度及特异度。[结果]恶性组胸腔积液CEA、CA199水平及阳性率均高于良性组（P<0.05）;恶性组血清CEA、CA199的检测水平均高于良性组（P<0.05)。胸腔积液CEA+CA199肿瘤标志物联合检测的敏感度、特异度及ROC曲线下面积分别为73.82%、69.7%和0.720,而胸腔积液CEA+CA199联合细胞形态学检查的敏感度、特异度及ROC曲线下面积更优,分别为85.23%、69.7%和0.777。[结论]联合测定胸腔积液中CA199、CEA水平和细胞形态学分析能提高良、恶性胸腔积液的鉴别诊断价值。     

胸水CEA、NSE、CYFRA21-1检测对恶性胸腔积液的诊断价值

目的:探讨癌胚抗原(CEA)、神经特异性烯醇化酶(NSE)、细胞角质蛋白19片断(CYFRA21-1)联合检测对恶性胸腔积液的诊断价值.方法:采用放射免疫法测定176例病人胸腔积液中上述指标的含量.结果:62例恶性胸腔积液(肺癌)组的测定值显著高于70例非恶性胸腔积液组的测定值(P＜0.01).CEA、NSE、CYFRA21-1在肺癌中的腺癌、小细胞癌、鳞癌的测定值最高,阳性率亦最高.两项联检NSCLC以CYFRA21-1、CEA阳性率较高,SCLC以NSE、CYFRA21-1阳性率较高.三项标志物联合检测诊断肺癌并恶性胸腔积液的敏感性显著高于单项检测和两项联检.结论:三者联检有助于恶性胸腔积液的诊断.在肺癌并恶性胸腔积液中,CEA对腺癌,NSE 对小细胞癌、CYFRA21-1对鳞癌有较高的敏感性.     

胸腔积液中肿瘤标志物检测在肺癌合并胸腔积液诊断中的应用

目的 探讨胸腔积液中癌胚抗原(CEA)、糖链抗原125(CA125)、糖链抗原199(CA199)、神经元特异性烯醇化酶(NSE)检测对肺癌合并胸腔积液的诊断价值.方法 采用化学发光法对30例肺癌合并胸腔积液患者与35例良性疾病合并胸腔积液患者的胸腔积液进行CEA、CA125、CA199、NSE测定,并根据受试者工作曲线(ROC)建立合理的临床判断界值.结果 肺癌患者胸腔积液中CEA、CA125、CA199、NSE的平均水平均明显高于良性疾病患者(P＜0.05).CEA、CA125、CA199、NSE的ROC曲线下面积分别为0.94、0.79、0.85、0.79,最佳临界值分别为16.0 μg·L-1、45.2 u·mL-1、39.3 u·mL-1、17.6 μg·L-1.CEA、CA125、CA199、NSE联合检测敏感度为96.7％,特异度为82.9％.结论 检测胸腔积液中CEA、CA125、CA199、NSE的水平对肺癌合并胸腔积液的诊断有重要价值,4种肿瘤标志物联合检测可提高诊断水平.     

肿瘤标志物联合检测在胸腹水性质鉴别中的临床应用

目的：探讨CEA、CA125、CYFRA21-1等8种肿瘤标志物检测在胸腹水鉴别诊断中的临床应用价值.方法：采用电化学发光法分别对176例患者的胸水和/或腹水进行癌胚抗原（CEA）、糖类癌抗原125 （CA125）、细胞角蛋白片段19（CYFRA21-1）等8项肿瘤标志物检测（其中恶性胸腹水81例,结核性胸腹水45例及不明原因胸腹水50例）,评价上述指标在鉴别胸腹水性质诊断中的灵敏度及特异性.结果：8项肿瘤标志物在良、恶性胸腹水中的表达水平具有显著性差异（P＜0.05）.恶性胸腹水中CEA、CA125、CYFRA21-1、NSE的水平及阳性率较高,分别为94%、81%、62%和52%.相关胸腹水肿瘤标志物联合检测对鉴别诊断不同良恶性胸腹水有统计学意义（P＜0.05）.结论：胸腹水中CEA、CA125、CYFRA21-1、NSE联合检测对良恶性胸腹水鉴别诊断有重要价值.     

胸水和血清CEA、CA125、CYFRA21-1、NSE和Pro-GRP联合检测对肺癌的诊断价值

目的:探讨联合检测肺癌胸水和血清中癌胚抗原(CEA)、癌抗原125(CA125)、细胞角蛋白19片段(CYFRA21-1)、神经原特异性烯醇化酶(NSE)和胃泌素释放肽前体(Pro-GRP)5 种肿瘤标志物水平在肺癌临床诊断中的应用价值,以期提高鉴别良恶性胸水的能力。方法:用电化学发光法检测93例肺癌患者和54例肺炎性疾病患者的血清及胸水标本CEA、CA125、CYFRA21-1、NSE和Pro-GRP水平。结果:癌性胸水组中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物平均水平与炎性胸水组比较,差别均有统计学意义(P<0.05);癌性胸水组中CEA、CYFRA21-1、CA125的含量远远高于炎性胸水组（20~600倍）(P<0.01)。肺癌胸水组中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物水平与肺癌血清组比较,差别均有统计学意义(P<0.05)。肺癌胸水组中CEA、CYFRA21-1、CA125的含量远远高于肺癌血清组（7~80倍）(P<0.01),相比与正常对照组更是有200倍以上的增高(P<0.01),因此胸水中CEA、CYFRA21-1、CA125百倍左右的升高提示恶性肿瘤的存在。将93例癌性胸水和血清分为腺癌、鳞癌和小细胞癌。腺癌、鳞癌和小细胞癌胸水组中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物含量明显高于炎性胸水组(P<0.01);腺癌胸水组中CEA含量明显高于鳞癌和小细胞癌(P<0.01);鳞癌胸水组中CYFRA21-1含量明显高于腺癌和小细胞癌(P<0.01);小细胞癌胸水组中NSE和Pro-GRP含量明显高于腺癌和鳞癌(P<0.01)。CA125含量在胸水组中腺癌、鳞癌含量明显高于小细胞癌(P<0.01)。5 种标志物单项及联合检测的灵敏度肺癌胸水组均高于肺癌血清组,肺癌胸水中5项联合检测后灵敏度可达99.11%。结论:肺癌组胸水中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物联合检测有利于良恶性胸水的鉴别诊断,联合检测可以提高肺癌诊断的灵敏度,当肿瘤标志物显著升高时,CEA可作为肺腺癌的肿瘤标志物;CYFRA21-1可作为肺鳞癌的肿瘤标志物;NSE和Pro-GRP可作为小细胞癌的肿瘤标志物;CA125可作为非小细胞肺癌的肿瘤标志物。     

Diagnostic utility of CYFRA 21-1, carcinoembryonic antigen, CA 125, neuron specific enolase, and squamous cell antigen level determinations in the serum and pleural fluid of patients with pleural effusions.

BACKGROUND: To the authors' knowledge the role of tumor marker determination in the differential diagnosis of pleural effusions has not been established definitively. The current article reports the results of a study of CYFRA 21-1, carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), squamous cell antigen (SCC), and neuron specific enolase (NSE) in the serum and pleural fluid of patients with pleural effusions of diverse etiologies. METHODS: One hundred forty-six patients with pleural effusions (43 malignant, 47 tuberculous, 32 miscellaneous benign, and 24 paramalignant) were studied prospectively. Levels of CYFRA 21-1, CA 125, CEA, NSE, and SCC were measured by radioimmunoassay in the pleural fluid in all patients and in the serum in 118 patients. RESULTS: There were no significant differences between the serum and pleural fluid levels of tumor markers with the exception of CA 125, which was higher in the pleural fluid. With maximum specificity, the highest sensitivity in the diagnosis of pleural malignancy was obtained with a combination of CYFRA 21-1 (with a cutoff value of 150 U/L), CEA (with a cutoff value of 40 ng/mL), and CA 125 (with a cutoff value of 1000 ng/mL) in pleural fluid. NSE and SCC added no diagnostic value. The simultaneous use of tumor markers and cytology in pleural fluid increased the sensitivity from 55.8% to 81%. CONCLUSIONS: These findings suggest that a combination of CYFRA 21-1, CEA, and CA 125 in the pleural fluid can be a useful addition to pleural cytology in the diagnosis of malignant pleural effusion.     

Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions

Carcinoembryonic antigen (CEA), carbohydrate antigens 15-3, 19-9 and 72-4 (CA 15-3, CA 19-9 and CA 72-4), cytokeratin 19 fragments (CYFRA 21-1), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) were evaluated in pleural fluid for the diagnosis of malignant effusions. With a specificity of 99%, determined in a series of 121 benign effusions, the best individual diagnostic sensitivities in the whole series of 215 malignant effusions or in the subgroup of adenocarcinomas were observed with CEA, CA 15-3 and CA 72-4. As expected, a high sensitivity was obtained with SCC in squamous cell carcinomas and with NSE in small-cell lung carcinomas. CYFRA and/or CA 15-3 were frequently increased in mesotheliomas. Discriminant analysis showed that the optimal combination for diagnosis of non-lymphomatous malignant effusions was CEA + CA 15-3 + CYFRA + NSE: sensitivity of 94.4% with an overall specificity of 95%. In malignant effusions with a negative cytology, 83.9% were diagnosed using this association. The association CYFRA + NSE + SCC was able to discriminate adenocarcinomas from small-cell lung cancers. Regarding their sensitivity and their complementarity, CEA, CA 15-3, CYFRA 21-1, NSE and SCC appear to be very useful to improve the diagnosis of malignant pleural effusions.     

Diagnostic value of CEA, CA 15-3, CA 19-9, CYFRA 21-1, NSE and TSA assay in pleural effusions

The aim of this study was to evaluate the individual and combined diagnostic utility of six tumor markers in patients with pleural effusion. Pleural and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), cytokeratin fragment 19 (CYFRA 21-1), neuron-specific enolase (NSE) and total sialic acid (TSA) were assayed in 74 patients with pleural effusions (44 malignant and 30 benign). All tumor markers except TSA and NSE were increased in both serum and pleural fluid of patients with malignant diseases. Using the cut-off values 3 ng/ml, 14 U/ml, 5 U/ml, 8 ng/ml and 70 mg/dl for pleural fluid CEA, CA 15-3, CA 19-9, CYFRA 21-1 and TSA, respectively, the sensitivity (%) and specificity (%) of these tumor markers were as follows: CEA; 52/77, CA 15-3; 80/93, CA 19-9; 36/83, CYFRA 21-1; 91/90, TSA; 80/67, for differentiating malignant effusions from benign. When CA 15-3 and CYFRA 21-1 combined, the sensitivity and specificity were increased (100 and 83%, respectively). Classifying the malignant effusions as bronchial carcinoma and malignant pleural mesothelioma, CEA was shown to have the highest sensitivity and specificity (88 and 90%, respectively) while the combination of CEA with other tumor markers increased sensitivity but decreased specificity. According to our results, tumor markers are not suitable for the differential diagnosis of malignancy.     

Diagnostic value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and review of the literature

Levels of tumor markers in pleural effusions may help to establish the diagnosis of pleural malignancy, but the precise diagnostic value of each marker remains unclear. The aim of this study was to assess the diagnostic value of five common pleural fluid tumor markers, carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, cancer antigen (CA) 15-3, CA 19-9, and CA 125, and to review the literature from the past 15 years. Pleural fluid samples were collected prospectively from 116 patients and assayed for CEA, CYFRA 21-1, CA 15-3, CA 19-9, and CA 125 levels. A MEDLINE search of the English-language literature from the past 15 years was also done. Effusions were classified as benign or malignant on the basis of their definitive pathologic or cytologic diagnoses. The levels of all pleural tumor markers were statistically significantly higher in the malignant group than in the benign group. The marker with the highest accuracy was CEA (85.3%); CA 15-3, CYFRA 21-1, and CA 19-9 had similar accuracies (75.2%, 72.4%, and 71.5%, respectively), and CA 125 had the lowest accuracy (40.5%). On univariate analysis, tumor-marker combinations did not result in a greater accuracy than that of CEA alone. On multivariate logistic regression, CA 15-3 and CYFRA 21-1 were significant predictors of malignancy. Among the nine reports in the literature comparing 11 different tumor markers, CEA, CA 15-3, and CYFRA 21-1 yielded the best results. We conclude that pleural fluid analysis should include CEA for the diagnosis of malignancy. CA 15-3 and CYFRA 21-1 may serve as alternative options.     

六种肿瘤标志物在肺癌胸腔积液中的诊断价值

目的通过对胸腔积液和血清中6种肿瘤标志物的检测及胸腔积液脱落细胞学检查,探讨各指标在肺癌胸腔积液中的诊断价值。方法应用化学发光法和酶联免疫分析法测定50例肺癌和30例肺良性疾病患者的胸腔积液和血清中的癌胚抗原（CEA）、糖类抗原19—9（CA19—9）、鳞状细胞癌抗原（SCC）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19片段（CYFRA21—1）、胃泌素前体释放肽（ProGRP）水平,同时对胸腔积液标本进行脱落细胞学检查,并根据受试者工作特性曲线（ROC）建立合理的临床判断临界值。结果肺癌患者胸腔积液中6种肿瘤标志物水平均高于肺良性疾病者,其中CEA、CA19-9、CYFRA21—1、ProGRP水平显著高于肺良性疾病组（P〈0．05）。胸腔积液CEA、血清CYFRA21—1及CEA含量在胸腔积液与血清中的比值（P／S）在各组中的ROC曲线下面积最大。结论胸腔积液CEA、血清CYFRA21—1及CEA的P／S值在鉴别良、恶性胸腔积液中有一定的辅助诊断价值,胸腔积液CEA的诊断价值最大。     

肿瘤标志物联合检测在良恶性胸腔积液鉴别诊断中的价值

 目的　探讨胸腔积液4种肿瘤标志物联合检测在良恶性胸腔积液鉴别诊断中的价值。方法　采用电化学发光免疫法检测126例胸腔积液患者（其中恶性组52例,良性组74例）癌胚抗原（CEA）、糖类抗原125（CA125）、糖类抗原15-3（CA15-3）和细胞角蛋白片段19（CYFRA21-1）水平, 并计算上述指标单独和与CEA联合检测在诊断中的敏感度、特异度、准确度和约登指数（YI）。结果　恶性组4种肿瘤标志物水平均明显高于良性组（P＜0.01）。单项检测各种肿瘤标志物的敏感度以CA125最高（90.4 %）,特异度以CYFRA21-1最高（79.7 %）,诊断准确度以CEA和CYFRA21-1最高（71.4 %）,YI以CEA最高（0.41）。联合检测较单项检测敏感度、准确度和YI明显提高,其中CEA、CYFRA21-1和CA15-3三项联合效果最好,敏感度为92.3 %,特异度为78.4 %,准确度为84.1 %,YI值最高为0.71。四项联合敏感度为94.2 %,特异度为75.7 %,准确度为83.3 %,YI值为0.70,与三项联合结果相比差异无统计学意义（P＞0.05）。结论　单项检测的诊断价值有限,CEA、CYFRA21-1和CA15-3三项联合效果最好、最经济,可指导患者恰当选择进一步的侵入性检查手段。