New approaches in the diagnostic procedure of malignant pleural effusions

The content of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (Ca 19-9), carbohydrate antigen 15-3 (Ca 15-3) and the expression of LewisY related carbohydrate antigens in benign and malignant pleural effusion were determined. These included 35 malignant pleural effusions: 13 breast cancers, 12 lung cancers (6 squamous cell carcinomas, 5 adenocarcinomas and 1 microcytoma), 2 mesotheliomas, 1 epithelioma, 1 kidney cancer, 1 hepatocarcinoma, 1 colon carcinoma, 3 lymphomas, 1 osteosarcoma and 9 benign pleural effusions. We showed that pleural fluid content of CEA, Ca 19-9 and Ca 15-3 were higher in malignant than in benign effusions. However CEA levels in squamous lung cancers were very high in both serum and pleural fluids whereas its levels were only slightly above the cut-off in breast cancers and in lung adenocarcinomas. Serum and pleural fluid Ca 15-3 values were higher in breast and in lung cancers with the highest values in the patients with breast cancer. Furthermore, the LewisY related carbohydrate antigens, evaluated by the reactivity of the cell extracts to MAb B3, were expressed only in breast cancers. These data suggest that pleural fluid content of CEA, and Ca 15-3 associated with the immunoblotting of cell extracts with MAb B3 appear to be very useful to improve the diagnosis of malignant pleural effusions.     

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。     

Matrix metalloproteinase-2 and matrix metalloproteinase-9 type IV collagenases in serum of patients with pleural effusions

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are essentially involved in the turnover of the extracellular matrix (ECM). Recently, several MMPs were implicated in creating an environment that supports the initiation and maintenance of tumor growth. We verified MMP activity in the sera of patients with pleural effusions by gelatin zymography. Of these patients, 22 had malignant pleural effusion, consisting of 11 breast carcinomas and 11 lung carcinomas (7 squamous cell carcinomas and 4 adenocarcinomas), and 8 patients had benign effusions. The sera of 25 healthy subjects were used as controls. Zymography analysis showed three major gelatinolytic bands of 72, 92 and 220 kDa. The MMP-9/MMP-2 ratio was enhanced in cancer patients compared with benign diseases and healthy individuals. Furthermore, we determined the circulating levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (Ca 19-9), carbohydrate antigen 15-3 (Ca 15-3). The serum levels of Ca 15-3 were above the cut-off levels in several cancer patients. No correlation between gelatinolytic activity and high tumoral marker values was found.     

Clinical evaluation of various tumor markers in pleural effusion and in the serum

Various tumor markers and enzymes in the pleural effusion and serum have been measured in 47 patients with carcinoma and in 43 patients with benign disease, by means of a radioimmunoassay and biochemical methods. CEA in the pleural effusion showed a high specificity and sensitivity for the detection of the malignancy. In patients with a lung cancer, measurement of the NSE in the serum was more useful than in the pleural effusion. Further, both CA19-9 and SCC in the pleural effusion showed a high specificity in a differential diagnosis of cancer and benign diseases. On the other hand, CA 125, TPA and IAP in the pleural effusion and in the serum showed a high sensitivity, but a low specificity for diagnosing the malignancy. The levels of ADA were significantly higher in tuberculous pleural effusions than in carcinomatous effusions. Therefore, this suggests that measurement of the various tumor markers in both the pleural effusion and in the serum is useful in achieving a differential diagnosis of malignant and benign diseases.     

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。     

胸腔积液中肿瘤坏死因子、癌胚抗原和神经元特异性烯醇化酶的检测及诊断价值研究

目的探讨检测胸水中肿瘤坏死因子（TNF-α）、癌胚抗原（CEA）和神经元特异性烯醇化酶（NSE）对胸腔积液的诊断价值。方法采用电化学发光酶免疫分析法检测59例结核性胸水和48例肺癌性胸水患者胸水中TNF-α、CEA和NSE水平。结果结核性胸水中TNF-α水平显著高于肺癌性胸水（P〈0.05）。肺癌性胸水中CEA和NSE明显高于结核性胸水（P〈0.01）。肺腺癌胸水中CEA升高最明显,非小细胞肺癌胸水中NSE升高最显著。联合检测CEA及NSE,诊断敏感度92.0%,准确度86.3%。结论检测TNF-α、CEA和NSE对结核性胸水和肺癌性胸水的诊断及鉴别诊断有较高的临床价值,联合检测胸水CEA和NSE可提高肺癌诊断敏感度。     

Tumor markers in pleural effusion diagnosis

In order to discriminate between malignant and benign effusions, the values of carcinoembryonic antigen (CEA), ferritin, beta2-microglobulin (BMG), acid-soluble glycoprotein (ASP), tissue polypeptide antigen (TPA), adenosine deaminase (ADA), and immunosuppressive acidic protein (IAP) were measured in the pleural fluid of 54 patients with lung cancer, 20 with malignancies other than lung cancer, 18 with tuberculous pleurisy, and 22 with benign diseases other than tuberculosis. CEA levels in malignant effusions were significantly higher than those in benign effusions. At a cutoff level of 5 ng/ml, 68% of the patients with lung cancer and 44% of the patients with other malignancies showed elevated pleural fluid CEA levels. In 13 lung cancer cases with negative pleural fluid cytology, nine cases had elevated pleural fluid CEA levels. The mean pleural fluid BMG level of patients with benign diseases was significantly higher than that of patients with malignant diseases, but there was a marked overlap between those with malignant and benign diseases. No significant differences were found in the pleural fluid ferritin, ASP, TPA, and IAP levels between malignant and benign conditions. ASP and IAP pleural fluid levels showed significant correlations with the pleural fluid C-reactive protein (CRP) concentrations suggesting that they also reflect inflammatory activity. The mean ADA activity in tuberculous effusion was significantly higher than that resulting from other causes of pleural effusion.     

Diagnostic value of tumor markers for differentiating malignant and benign pleural effusions of Iranian patients

In order to evaluate the diagnostic yield of tumor markers in differentiating malignant and benign pleural effusions, we carried out a prospective study in a group of Iranian people. Pleural and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), neuron-specific enolase (NSE) and cancer antigen 125 (CA 125) were assayed prospectively in patients with pleural effusion (40 malignant and 37 benign). The highest sensitivity was obtained with a combination of CA 15-3 in serum, and CA 15-3 and CEA in pleural fluid (80%), also with combination of CA 15-3 in serum, and CA 15-3, NSE and CEA in pleural fluid (80%). The highest specificity was obtained with combination of CA 15-3 in serum, and CA 15-3 and NSE in pleural fluid (100%), and also with combination of CA 15-3 in serum, and CA 15-3, NSE and CEA in pleural fluid (100%).     

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。     

肺癌单克隆抗体检测良,恶性胸腔积液的评价

为了评价肺癌单克隆抗体检测良恶性胸腔积液的诊断与鉴别诊断价值，同步采集临床上明确诊断的６３例良恶性胸腔积液患者的胸水和血清，以及１０例正常人的血清，进行肺癌单抗金标免疫斑点渗透法的检测，并与癌胚抗原的检测比较。结果显示：恶性胸腔积液组肺癌单抗金标免疫斑点渗透法和癌胚抗原的阳性率明显高于良性胸腔积液组及正常组（Ｐ＜０．０１），而且肺癌单抗金标免疫斑点渗透法检测的阳性率高于癌胚抗原。在恶性胸腔积液中，肺癌单抗金标免疫斑点渗透法的灵敏度和特异度分别为６５．１％和１００．０％，癌胚抗原的灵敏度和特异度分别为５３．５％和９５．０％，两项指标联合检测的灵敏度和特异度分别为７６．７％和９５．０％。说明肺癌单抗金标免疫斑点渗透法对良恶性胸腔积液有鉴别诊断价值，而且优于癌胚抗原；两项指标联合检测可以提高对恶性胸腔积液的诊断符合率。     

联合检测EGFR、CEA对恶性胸腔积液的诊断价值

目的:评价联合检测胸腔积液患者的胸水细胞块表皮生长因子受体（epidermal growth factor receptor,EGFR）基因拷贝数,以及胸水、血清CEA水平对良恶性胸腔积液鉴别诊断的价值。方法:应用荧光原位杂交技术（Fish法）检测恶性胸腔积液（n=35）、良性胸腔积液（n=30)组患者胸水细胞块EGFR基因拷贝数水平。采用电化学发光全自动生化分析仪检测胸水及血清中CEA水平,根据受试者工作特性曲线（ROC）选取最佳灵敏性和特异性的点作为临界值,评价CEA及联合检测EGFR基因拷贝数对良恶性胸腔积液的诊断价值。结果:35例恶性胸腔积液完成Fish检测。恶性胸腔积液中15例阴性,20例阳性,阳性率为57.1％。其中13例为EGFR基因高度多体性,7例为EGFR基因扩增。肺腺癌16例中,EGFR基因高度多体性、扩增14例,肺腺癌扩增率为87.5％;肺鳞癌14例中,EGFR基因簇状扩增3例(21.4％),点状扩增3例(21.4％),无扩增8例(57.1％),肺鳞癌扩增率为42.9％。腺癌Fish阳性率(87.5％)高于鳞癌(42.9％）,P<0．01。30例良性胸腔积液中有1例脓胸患者EGFR Fish检测阳性,阳性率为3.3%,余检测结果均阴性。恶性胸腔积液患者胸水及血清CEA分别为（220.9±71.65）ng/ml、(18.11±11.38）ng/ml,显著高于良性胸腔积液组（2.31±1.29)ng/ml、(1.67±1.06）ng/ml,差异有统计学意义（P<0.01）。其中,恶性胸腔积液胸水CEA明显高于血清CEA,而良性胸腔积液组中,胸水CEA与血清CEA无明显差异。肺腺癌所致胸水及血清CEA分别为（441.02±102.65)ng/ml、(32.87±28.66）ng/ml,鳞癌所致胸水及血清CEA分别为（28.75±21.39）ng/ml、（5.99±5.32）ng/ml,腺癌显著高于鳞癌,差异有统计学意义（P<0.01）。比较胸水EGFR、CEA对良恶性胸腔积液诊断的效能,两者之间无明显差异（P=0.453＞0.05）。Spearman相关性分析胸水EGFR同CEA之间存在显著正相关。结论:EGFR在恶性胸腔积液的形成中起重要作用,通过Fish技术检测胸水细胞块EGFR基因拷贝数可行,其敏感性为57.1%。对肺腺癌导致恶性胸腔积液的诊断敏感性为87.5%。CEA（临界值5.0ng/ml）在恶性胸腔积液及血清中显著高于良性,其中胸水CEA检测诊断敏感性为65.7%,而在腺癌中为87.5%,其在胸水及血清中的比值＞1.5有助于恶性胸腔积液的诊断。EGFR基因突变阳性与肿瘤标记物CEA阳性表达呈正相关,尤见于肺腺癌患者,两者联合检测可提高诊断性试验的准确性。     

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。     

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 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.     

Tnp-alpha determination in serum and pleural effusion in patients with lung-cancer

The relationship between Tumor Necrosis Factor-alpha (TNF-alpha) in the serum and pleural fluid of lung cancer patients and the extent and the histological cell type was studied. TNF-(a)lpha level was determined in the serum of 68 patients with lung cancer [51 non-small cell lung cancer (NSCLC) and 17 small cell lung cancer (SCLC)] and in pleural fluid of 30 patients with lung cancer (22 NSCLC, 11 of them positive for neoplastic cells and 8 SCLC, 7 of them positive). Sera of 31 healthy subjects and the pleural fluid of 15 non-malignant pleural effusions were tested as controls. TNF-alpha serum level was increased in patients with lung cancer (healthy subjects 7.8+/-3.3 pg/ml; lung cancer 16.2+/-9.1 pg/ml), in NSCLC as well as SCLC and a relationship with the extent of the disease was found in both the histological types. In pleural fluid, no differences of TNF-alpha level were observed between neoplastic and benign inflammatory effusion, between SCLC and NSCLC or between cases positive and negative for the presence of neoplastic cells. Serum TNF-alpha may be an indicator of tumour burden; conversely, TNF-alpha in pleural fluid, was unable to discriminate between neoplastic and benign effusion.     

TPS in breast cancer--a comparative study with carcinoembryonic antigen and CA 15-3.

The serum levels of tissue polypeptide antigen were determined using the M3 monoclonal antibody (TPS) and compared with the serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen 15-3 (CA 15-3) in 96 patients with benign breast tumors, in 25 breast cancer patients with no evidence of disease, in 139 preoperative breast cancer patients and in 298 samples of 25 breast cancer patients during therapy monitoring (4-22 samples per patient). The 95th percentile of TPS in 89 apparently healthy females was 51 U/l. The 95th percentile of TPS in patients with benign breast tumors was 55 U/l. The maximum TPS level in breast cancer patients with no evidence of disease was 56 U/l. In preoperative breast cancer the number of patients with TPS levels above the 95th percentile of TPS in benign breast tumors was significantly higher in stage III breast cancer as compared with stage I+II. This was not established for CEA and CA 15-3. During therapy monitoring TPS followed the course of the disease faster than CEA and CA 15-3 in patients with bone metastases, liver metastases, lung metastases and pleural effusion, with one exception. TPS levels could be correlated with progression of disease in patients with normal and steady levels of CEA and/or CA 15-3.     

Clinical evaluation of four tumor markers in malignant and benign pleural effusions.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy.     

Diagnostic significance of the tumour markers CEA, CA 15-3 and CA 125 in malignant effusions in breast cancer

Concentrations of the tumour-associated antigens CEA, CA 15-3 and CA 125 were determined in serous effusions (EF) from patients (pts) with breast cancer. As controls, serous effusions from patients with benign and other malignant diseases were used. The EF levels were also compared with those of serum. CA 15-3 was elevated (greater than 35 U/ml) in 65.7% of breast cancer EF, in 39.3% of EF in various other malignant diseases and in 0% of benign EF. CEA was elevated (greater than 9 ng/ml) in 37.5% of breast cancer EF, in 17.9% of EF of various other malignant diseases and in 27% of benign EF. CA 125 was elevated (greater than 35 U/ml) in 93.8% of breast cancer EF, in 78.6% of EF of various other malignant diseases and in 58.8% of benign EF. There was a statistically significant correlation between EF and serum values for the markers studied. Sensitivity and specificity for CA 15-3 were 65.7% and 76.6%, for CEA 37.5% and 77.7% and for CA 125 93.8% and 28.7%, respectively. CA 15-3 is a marker with definite diagnostic accuracy compared to CEA and CA 125 in breast cancer EF. CA 125 appears to derive from proliferating mesothelia rather than cancer cells alone and occurs in a broad spectrum of malignant as well as benign EF. The above markers should not be used alone for diagnosis of breast cancer in patients with serous effusions.     

Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions.

CYFRA 21-1 assay, measuring cytokeratin 19 fragments, was compared with carcinoembryonic antigen (CEA) assay, as an addition to cytological analysis for the diagnosis of malignant effusions. Both markers were determined with commercial enzyme immunoassays in pleural fluid from 196 patients. Cytological analysis and/or pleural biopsy confirmed the malignant origin of the effusion in 99 patients (76 carcinomas, nine pleural mesotheliomas and 14 non-epithelial malignancies). Effusions were confirmed as benign in 97 patients (33 cardiac failures, 39 infectious diseases--including 12 tuberculosis-- and 25 miscellaneous effusions). Both markers were significantly higher in malignant than in benign effusions. All the patients with non-epithelial malignancies presented CYFRA and CEA values lower than the 95% diagnostic specificity thresholds (100 and 6 ng ml(-1) respectively). The diagnostic sensitivity in the group of carcinomas and mesotheliomas was similar for CYFRA (58.8%) and CEA (64.7%). However, CEA had a significantly higher sensitivity in carcinomas (72.4% vs 55.3%), while CYFRA had a clearly higher sensitivity in mesotheliomas (89.9% vs 0%). Interestingly, 12 out of the 16 malignant effusions with a negative cytology were CEA and/or CYFRA positive. Regarding their high diagnostic sensitivity and their complementarity, CEA and CYFRA appear to be very useful for the diagnosis of malignant pleural effusions when cytology is negative.