免疫细胞化学染色检查协助鉴别浆膜腔积液中转移性腺癌原发部位

目的：探讨一组鉴别浆膜腔积液中转移性腺癌原发部位的抗体。方法：对31例浆膜腔积液转移性腺癌制备细胞蜡块切片作TTF-1、CA125、CK7、CK20免疫细胞化学染色,这些病例经组织学或结合临床资料证实：肺腺癌15例、卵巢腺癌10例、胃肠癌6例。结果：肺腺癌的阳性表达分别是TTF-1（73.3%）、CA125（26.7%）、CK7（73.3%）、CK20（0%）,卵巢腺癌的阳性表达分别是TTF-1（0%）、CA125（70.0%）、CK7（100.0%）、CK20（0%）,胃肠腺癌的阳性表达分别是TTF-1（0%）、CA125（16.7%）、CK7（0%）、CK20（100.0%）。TTF-1在肺腺癌的表达具有高度敏感性（73.3%）及特异性（100%）,CA125在卵巢腺癌的表达也有较高的敏感性（70.0%）,CK7（-）/CK20（＋）在胃肠腺癌的表达100%。结论：联合检测TTF-1、CA125、CK7、CK20能有效鉴别浆膜腔积液中来自肺、卵巢、胃肠道的腺癌。     

胸腔积液脱落细胞免疫组化染色对肿瘤来源鉴别诊断价值的探讨

目的:评估波形蛋白(VIM)、神经特异度钙结合蛋白(CR)、间皮细胞(MC),细胞角蛋白7(CK7)和甲状腺转录因子-1(TTF-1)免疫组化染色在转移性肺腺癌和恶性间皮瘤鉴别诊断中的价值.方法:收集经病理学确诊的恶性胸腔积液患者82例,选取其中的胸膜转移性肺腺癌和恶性胸膜间皮瘤患者纳入分析.评估TTF-1、CK7、Vimentin、MC和Calretinin 5项指标对胸膜转移性肺腺癌和恶性胸膜间皮瘤的诊断灵敏度和特异度.结果:VIM(x2 =4.99,P=0.014)、CR(x2 =23.74,P=0.01)和MC(x2 =13.08,P=0.001)的表达在恶性胸膜间皮瘤的表达高于胸膜转移性肺腺癌.而TTF-1(x2 =21.67,P＜0.01)和CK7(x2 =18.12,P＜0.01)在胸膜转移性肺腺癌表达高于恶性胸膜间皮瘤.对于恶性间皮瘤的诊断,VIM的灵敏度为72.7％(8/11),特异度为64.4％ (29/45);CR的灵敏度为90.9％ (10/11),特异度为84.4％(38/45);MC的灵敏度为72.7％ (8/11),特异度为82.2％ (37/45).对于胸膜转移性肺腺癌的诊断,CK7的灵敏度为95.6％ (43/45),特异度为54.5％ (6/11);TTF-1的灵敏度为82.2％(37/45),特异度为90.9％(10/11).结论:胸腔积液脱落细胞的TTF-1、CK7、Vimentin、MC和Calretinin免疫组化染色对恶性胸膜间皮瘤和胸膜转移性肺腺癌的鉴别具有较高价值.     

免疫组化对恶性胸膜上皮型间皮瘤与肺腺癌鉴别诊断价值的探讨

目的:探讨免疫组化对恶性胸膜上皮型间皮瘤与肺腺癌鉴别诊断的价值。方法:用免疫组化SP法检测27例胸膜上皮型恶性间皮瘤和30例肺腺癌组织中,Calretinin、WT1、D2-40、CK5/6、CEA、MOC-31和TTF-1的表达情况,并应用受试者工作曲线(ROC)对检查结果分析,选择更合适的一组抗体用于恶性间皮瘤与肺腺癌的鉴别诊断。结果:Calretinin、D2-40、WT-1、CK5/6、CEA、MOC-31和TTF-1在恶性间皮瘤组织中的阳性表达率分别为92.5%(25/27)、92.5%(25/27)、96.3%(26/27)、77.8%(21/27)、11.1%(3/27)、0(0/27)和37.0%(10/27);在腺癌组织中的阳性率分别为13.3%(4/30)、6.7%(2/30)、10.0%(3/30)、26.7%(8/30)、90.0%(27/30)、83.3%(25/30)和96.7%(29/30)。间皮瘤阳性标志Calretinin、D2-40、WT1和CK5/6的ROC曲线下面积(AUC)值分别为0.896、0.930、0.931和0.756,腺癌标志CEA、TTF-1和MOC-31的AUC值分别为0.894、0.917和0.798。结论:免疫组化是鉴别恶性间皮瘤与腺癌最好的方法,Calretinin、WT1、D2-40、CEA和TFF-1是较为理想的标志,可作为恶性间皮瘤和腺癌鉴别诊断中的首选抗体。     

细胞块制片免疫组化对胸腹腔积液转移性腺癌的诊断价值

目的 探讨细胞块制片免疫组化对胸腹腔积液转移性腺癌的诊断价值.方法 收集胸腹腔积液患者100例,经过穿刺法获取胸腹腔积液标本100 ml,病理检查,给予常规涂片和细胞块制片,均联合免疫组化法,比较两种检测方法相关蛋白阳性、阴性以及不确定性,计算细胞阳性率.结果 细胞块检测阳性率为48.0%,高于常规检测的34.0%,不确定性比例为0,低于常规的22.0%(P<0.05);两种方法对良性组织检测结果显示:CK7、MOC-31、CD51、TTF-1、CEA、CA125、Ber EP4、NapsinA、E-cad均呈低表达,WT-1、Calretinin、CK5/6均呈高表达,恶性组织检测显示CK7、MOC-31、CD51、TTF-1、CEA、CA125、Ber EP4、NapsinA、E-cad均呈高表达,并且细胞块法阳性率均高于常规涂片法(P<0.05),WT-1、Calretinin、CK5/6均呈低表达;常规涂片对不确定组织检测结果:WT-1、Calretinin、CK5/6阳性率均较高,其他均为低阳性率,CK7、MOC-31、CD51、TTF-1、CEA、CA125、Ber EP4在转移性恶性肿瘤中阳性率均较高,并且细胞块阳性率均高于相应的常规涂片法(P<0.05).结论 细胞块制片免疫组化对胸腹腔积液转移性腺癌的诊断具有重要意义,各指标间联合可以判断肿瘤类型.     

D2-40联合Calretinin在恶性胸膜间皮瘤诊断及鉴别诊断中的价值

[目的]探讨D2-40在恶性胸膜间皮瘤诊断中的潜在价值.[方法]对余姚市人民医院及复旦大学附属中山医院病理科自1999—2009年诊断的31例恶性胸膜间皮瘤和30例肺腺癌进行回顾性分析并进行免疫组化检测,观察D2-40 、Calretinin 、CEA 、TTF-1在恶性间皮瘤和肺腺癌中的表达.[结果] D2-40、Calretinin在恶性胸膜间皮瘤中的灵敏度分别为80.6％、83.9％,特异性分别为93.3％、86.7％,两者联合诊断的灵敏度93.5％,其中上皮型间皮瘤为100.0％.CEA、TTF-1在肺腺癌中的灵敏度分别为90.0％、83.3％,特异性分别为87.1％和100.0％.[结论]D2-40联合Calretinin可以提高恶性胸膜间皮瘤鉴别诊断的准确率.D2-40、Calretinin 、CEA、TTF-1联合检测是鉴别恶性胸膜间皮瘤和肺腺癌的一组有价值的抗体.     

免疫组化在胸膜上皮性恶性肿瘤鉴别诊断中的价值

背景与目的 胸膜上皮性恶性肿瘤鉴别诊断难度较大,本文旨在探讨免疫组化在胸膜恶性间皮瘤与转移性肺腺癌鉴别诊断中的作用.方法 用免疫组化S-P法检测56例胸膜上皮性恶性肿瘤中波形蛋白、间皮细胞(MC)、钙结合蛋白(CR)、甲状腺转录因子-1(TTF-1)、癌胚抗原(CEA)、表面活性蛋白-B(Sp-B)、细胞角蛋白(CK)的表达情况.结果 用免疫组化方法确定56例胸膜上皮性恶性肿瘤中恶性间皮瘤24例,转移性肺腺癌22例.波形蛋白、MC、CR、TTF-1、CEA、Sp-B在恶性间皮瘤与转移性肺腺癌中表达差异具有显著性(P＜0.001或P＜0.002).结论 用免疫组化方法鉴别胸膜恶性间皮瘤与转移性肺腺癌,波形蛋白、MC、CR、TTF-1、CEA、Sp-B是较为理想的标志物.     

探讨CK7 CK20和TTF-1在判断转移性腺癌原发病灶中的应用价值

  目的  了解CK7、CK20及TTF-1在腺癌中的表达情况, 探讨联合应用这3种标志物对判断转移性腺癌原发部位的价值。  方法  采用组织芯片和免疫组织化学的  方法  , 检测CK7、CK20与TTF-1在229例腺癌及10例食管鳞癌组织中的表达。  结果  3种抗体在不同组织来源肿瘤中的表达可以组合成8种模式: CK7+/CK20-/TTF-1+: 甲状腺乳头状癌阳性率较高(50%); CK7+/CK20-/TTF-1-: 涎腺腺癌(94.44%)、乳腺小叶癌(85.71%)、卵巢浆液性癌(71.43%)、胆囊腺癌(63.64%)、宫颈腺癌(61.54%), 阳性率较高; CK7+/CK20+/TTF-1+: 阳性率均不高; CK7+/CK20+/TTF-1-: 阳性率均不高; CK7-/CK20-/TTF-1+: 阳性率均不高; CK7-/CK20-/TTF-1-: 前列腺癌(100%)、食管鳞癌(100%)、肾透明细胞癌(90.90%), 阳性率较高; CK7-/CK20+/TTF-1+: 阳性率均不高; (CK7-/CK20+/TTF-1-: 肠腺癌(66.67%)阳性率较高;  结论  联合检测(CK7、CK20及TTF-1抗体有助于判断部分转移性腺癌的器官来源, 缩小原发肿瘤的搜寻范围。      

血清骨桥蛋白和CA125联合检测鉴别良恶性腹水

目的:探讨联合检测血清骨桥蛋白(OPN)和CA125在良恶性腹水中的诊断价值。方法:取39例恶性腹水患者、48例结核性腹水患者及40例健康妇女血清样品,分别用双抗体夹心酶联免疫吸附法(ELISA)及微粒子化学发光法测定其OPN和CA125水平,观察其在诊断良、恶性腹水时的敏感性和特异性。结果:恶性腹水患者血清OPN水平明显高于结核性腹水患者及健康妇女组。OPN检测恶性腹水的敏感度、特异度分别为84.6%、95.0%;CA125检测敏感度、特异度为76.9%、87.5%;联合检测敏感度97.4%、特异度为95.0%。联合检测OPN、CA125较单独检测OPN及CA125其敏感度高(P<0.05);特异度无明显差异。结论:OPN与CA125联合测定是鉴别卵巢癌和结核性腹水的有效方法,联合检测CA125可提高其临床应用价值。     

联合检测E-cadherin、GEA及Calretinin在浆膜腔积液细胞学鉴别诊断中的意义

背景与目的:浆膜腔积液中转移性腺癌细胞、恶性上皮型间皮瘤细胞和反应性间皮细胞的形态有不少相似之处,有时仅凭形态学特征不能做出准确诊断.近年来免疫细胞化学在这方面得到较多应用,但国内报道仅局限于用CK、EMA、CEA、Vim和HBME-1几种抗体,而且不能较好地进行细胞学的鉴别诊断.本研究旨在探讨联合检测E-cadherin、CEA及calretinin在浆膜腔积液鉴别诊断中的应用价值.方法:选用浆膜腔积液标本共93例,其中胸水66例、腹水24例、心包积液3例.经组织学检查或结合临床资料证实的转移性腺癌55例、恶性上皮型间皮瘤6例、间皮细胞反应性增生32例.每例均制备HE染色的涂片和细胞块,并用细胞块切片作免疫细胞化学染色.结果:E-cadherin、CEA对诊断转移性腺癌的敏感性分别为85.5%(47/55)、78.2%(43/55),特异性分别为100%(38/38)、97.4%(37/38).E-cadherin 和CEA联合应用诊断浆膜腔积液转移性腺癌的阳性率为96.4%(53/55).Calretinin 对诊断间皮瘤和间皮细胞增生的敏感性和特异性分别为81.6%(31/38)和87.2%(48/55).结论:E-cadherin、CEA和calretinin是鉴别浆膜腔积液转移性腺癌细胞和间皮源性细胞有价值的一组抗体.     

胸腔积液中腺癌细胞甲状腺转录因子-1表达的定量研究

目的分析甲状腺转录因子-1(TTF-1)在胸腔积液腺癌细胞中的表达特点及规律,从量化角度探讨其作为判断胸水中转移性肺腺癌组织来源指标的临床应用价值。方法选用胸腔积液转移性腺癌48例,其中肺源性腺癌37例,非肺源性腺癌11例。每例均制备巴氏染色细胞涂片和离心沉淀石蜡包埋细胞蜡块切片,并对相应细胞蜡块切片行HE染色和TTF-1免疫组织化学染色。结果37例肺腺癌中28例表达TTF-1,11例肺外腺癌无1例表达TTF-1。胸水中肺源性腺癌细胞与非肺源性腺癌细胞TTF-1 PU值的比较差异具有显著性(p<0.01)。定量结果显示胸水中肺源性腺癌细胞与非肺源性腺癌细胞TTF-1 PU值的频数分布无重叠,以PU值大于8作为判断肺源性腺癌细胞的诊断阈值,以PU值小于6作为判断非肺源性腺癌细胞的诊断阈值,其诊断试验评价结果显示TTF-1对癌性胸水中肺腺癌细胞诊断的灵敏度为75.7%,特异度为100%。标准化阳性预告值为100%,标准化阴性预告值为80.43%,标准化准确度为87.84%。结论在排除甲状腺癌的可能性后,TTF-1作为胸腔积液细胞蜡块标本肺腺癌细胞的诊断性标志具有较高的特异性和敏感性,胸水中腺癌细胞TTF-1的PU值可作为判断肺源性与非肺源性腺癌细胞的特异性诊断指标。     

Utility of anti-L523S antibody in the diagnosis of benign and malignant serous effusions

BACKGROUND: Immunohistochemistry is helpful in distinguishing metastatic carcinoma from atypical mesothelial cells; however, it is not useful in differentiating atypical mesothelial cells from malignant mesothelial cells. K homolog domain containing protein overexpressed in cancer (KOC), a member of the insulin-like growth factor mRNA-binding protein (IMP) family, also known as L523S and IMP3, is expressed during embryogenesis and in various malignancies. Using a mouse monoclonal antibody (L523S) against KOC, KOC expression was investigated in malignant tumors and reactive mesothelial cells in serous effusions. METHODS: Seventy-six cases with paraffin-embedded pleural, pericardial, and peritoneal serous effusion cell blocks including 60 malignant serous effusions (11 malignant pleural mesotheliomas and 49 metastatic carcinomas) and benign pleural effusions (14 cases with reactive mesothelial cells and 2 cases with atypical cells with uncertain significance) were selected for immunohistochemical analysis with L523S, calretinin, and CK5/6. RESULTS: Immunohistochemical studies showed that positive staining for KOC of variable degrees of intensity was observed in 47 of 60 cases in malignant serous effusions including 10 of 11 mesotheliomas and 36 of 49 metastatic carcinomas. The associated reactive mesothelial cells were negative for KOC but positive for calretinin and CK5/6. All 11 malignant mesotheliomas exhibited positivity for calretinin, and 9 of 11 cases had CK5/6 staining. In addition, 16 cases that were originally diagnosed either as pleural effusions with reactive mesothelial cells (14) or atypical cells with uncertain significance (2) were also tested for KOC expression. Interestingly, 3 of 16 cases exhibited various degrees of positivity for KOC, 2 of which were diagnosed as lung adenocarcinoma with a recurrence after tumor resection and 1 as malignant pleural mesothelioma. CONCLUSIONS: Anti-L523S antibody is a useful marker for the detection of malignant cells in serous effusions and it can have significant utility in differentiating reactive mesothelial cells from malignant mesothelioma and metastatic carcinoma in combination with calretinin and CK5/6 staining.     

Utility of anti‐L523S antibody in the diagnosis of benign and malignant serous effusions

BACKGROUND.

Immunohistochemistry is helpful in distinguishing metastatic carcinoma from atypical mesothelial cells; however, it is not useful in differentiating atypical mesothelial cells from malignant mesothelial cells. K homolog domain containing protein overexpressed in cancer (KOC), a member of the insulin‐like growth factor mRNA‐binding protein (IMP) family, also known as L523S and IMP3, is expressed during embryogenesis and in various malignancies. Using a mouse monoclonal antibody (L523S) against KOC, KOC expression was investigated in malignant tumors and reactive mesothelial cells in serous effusions.

METHODS.

Seventy‐six cases with paraffin‐embedded pleural, pericardial, and peritoneal serous effusion cell blocks including 60 malignant serous effusions (11 malignant pleural mesotheliomas and 49 metastatic carcinomas) and benign pleural effusions (14 cases with reactive mesothelial cells and 2 cases with atypical cells with uncertain significance) were selected for immunohistochemical analysis with L523S, calretinin, and CK5/6.

RESULTS.

Immunohistochemical studies showed that positive staining for KOC of variable degrees of intensity was observed in 47 of 60 cases in malignant serous effusions including 10 of 11 mesotheliomas and 36 of 49 metastatic carcinomas. The associated reactive mesothelial cells were negative for KOC but positive for calretinin and CK5/6. All 11 malignant mesotheliomas exhibited positivity for calretinin, and 9 of 11 cases had CK5/6 staining. In addition, 16 cases that were originally diagnosed either as pleural effusions with reactive mesothelial cells (14) or atypical cells with uncertain significance (2) were also tested for KOC expression. Interestingly, 3 of 16 cases exhibited various degrees of positivity for KOC, 2 of which were diagnosed as lung adenocarcinoma with a recurrence after tumor resection and 1 as malignant pleural mesothelioma.

CONCLUSIONS.

Anti‐L523S antibody is a useful marker for the detection of malignant cells in serous effusions and it can have significant utility in differentiating reactive mesothelial cells from malignant mesothelioma and metastatic carcinoma in combination with calretinin and CK5/6 staining. Cancer (Cancer Cytopathol) 2008. © 2007 American Cancer Society.     

Diagnostic value of metabolic phenotypes in malignant pleural effusions: expression of GLUT1 and CAIX by immunocytochemistry

BACKGROUND:

The sensitivity of conventional cytology for the detection of malignant cells in pleural effusion is insufficient. GLUT1 and CAIX are the hallmarks of metabolic change in cancer cells. The aim of this study was to evaluate the usefulness of GLUT1 and CAIX expression to the detection of cancer cells in pleural effusions.

METHODS:

A total of 150 pleural effusions were subjected to immunocytochemical staining for GLUT1 and CAIX expression. According to their cytological diagnosis and etiology, these included 58 benign effusions, 38 probable malignant effusions, 7 atypical effusions, and 47 malignant effusions,.

RESULTS:

None of the benign effusions showed GLUT1 or CAIX expression, but probable malignant effusions and malignant effusions significantly expressed GLUT1 and CAIX with a positive result in 74.5% and 63.8% of the malignant effusions, respectively, with 100% specificity. When the combination of both markers was evaluated, GLUT1 and CAIX displayed a higher diagnostic performance, ie, a sensitivity of 76.6%, specificity of 100%, and accuracy of 89.5%. A statistically significant positive correlation between GLUT1 and CAIX expression was observed. In addition, 18% of cases with cells resembling mesothelial cell hyperplasia in probable malignant effusions and 71.4% of cases with atypical cells of uncertain significance in atypical effusions were highlighted on GLUT1 or/and CAIX immunocytochemical stains.

CONCLUSIONS:

Immunocytochemical staining for GLUT1 and CAIX may be a complementary tool for the detection of malignant pleural effusions and is helpful in distinguishing cancer cells from reactive mesothelial cells. A combination of GLUT1 and CAIX immunocytochemical staining can give a higher diagnostic performance. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.     

注射用重组改构人肿瘤坏死因子-NC（rhTNF-NC）治疗恶性肿瘤的Ⅱ期临床研究

【摘 要】目的 观察重组改构人肿瘤坏死因子-NC（rhTNF-NC）注射液单药治疗恶性肿瘤的临床疗效、不良反应以及对患者生活质量的影响。方法 入组的320例患者中,可进行疗效评价310例,脱落9例,剔除1例。310例患者中,恶性淋巴瘤71例,恶性胸腹水169例,恶性黑色素瘤18例,肺癌20例,肝癌12例,乳腺癌10例,结肠癌7例和肾癌3例。恶性淋巴瘤、恶性黑色素瘤、肺癌等实体肿瘤患者给予静脉注射rhTNF NC 60万～90万 IU／m2,最大剂量≤100万 IU／m2,1次／d,连用4周;恶性胸腹水患者予以胸腹腔注射rhTNF NC,剂量为200万～300万 IU／次,1～2次／周,连用2～3周;体表肿瘤（主要为恶性黑色素瘤）患者在rhTNF NC静脉给药的同时予以瘤体内或瘤床注射,推荐注射剂量为50万～100万 IU／次,2～3次／周。结果 可评价的患者310例,其中恶性胸腹水169例,实体肿瘤141例。实体瘤患者中获CR 2例,PR 21例,有效率（RR）为16.3％（23／141）,疾病控制率（DCR）为79.4％（112／141）。恶性淋巴瘤的RR为28.2％（20／71）,DCR为84.5％（60／71）;恶性黑色素瘤的RR为11.1％（2／18）,DCR为83.3％（15／18）;肺癌无CR病例,获PR 1例,MR 2例;肾癌获MR 1例;肝癌、结肠癌、乳腺癌均未见明显疗效。恶性胸腹水病例中获CR 15例,PR 102例,RR为69.2％（117／169）,DCR为98.8％（167／169）;其中,恶性胸水的RR为74.5％（105／141）,恶性腹水为42.9％（12／28）。全组患者治疗后的KPS评分较治疗前有显著提高（P=0.013）,特别是恶性胸水患者提高更为明显。主要不良反应为发热（38.8％）和寒战（23.5％）,绝大多数为1、2级。结论 注射用rhTNF-NC治疗恶性淋巴瘤和恶性胸腹水疗效明确,对肺癌、恶性黑色素瘤也有一定疗效,并能够明显改善各种癌症患者的生活质量,安全性良好。     

P53-immunoreactive cells in benign and malignant effusions: diagnostic value using a panel of monoclonal antibodies and comparison with CEA-staining

The diagnosis of malignancy in peritoneal and pleural effusions can be difficult, because activated mesothelial cells may resemble malignant cells. P53 mutations are the most frequent genetic changes in human cancer and translate into an overexpression of the p53 protein detectable by immunocytochemistry. In this study, we investigated the sensitivity and specificity of 4 different monoclonal antibodies (moAB) against p53 for the diagnosis of malignancy in effusions. We also compared p53 staining with CEA immunocytochemistry which previous work had established as a specific marker of malignancy in body cavity effusions. Normal and malignant cells from 28 benign and 52 malignant effusions (pleura and ascites) were examined by indirect immuno-alkaline phosphatase method. Four different moAB against p53 (PAB 1801, PAB 240, DO-1 and DO-7) and one moAB against CEA (CEA-84) were used. Antibodies p1801, p240 and DO-1 react with 52-75% of cases of effusions with malignant cells, but also with 38-80% of benign effusions. Only the antibody DO-7 and the CEA moAB show specificity for malignant cells reacting respectively with 20 (55%) of cases. A combination of these 2 markers does not enhance the sensitivity for the detection of tumor cells. No direct correlation between CEA and p53 immunostaining could be established. The sensitivity and specificity of staining p53 in malignant cells by immunocytochemistry depend strongly on the antibody used. Some p53 moAB are positive with reactive cells in ascites and pleural effusions. Currently, p53 staining of expressing cells does not improve the identification of malignant cells in comparison with CEA immunocytochemistry, but may help to screen for patients with p53 mutations.     

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.