Evaluation of a panel of molecular markers for the diagnosis of malignant serous effusions.
OBJECTIVE
Our main goal was to evaluate a panel of molecular markers for the detection of cancer cells in serous effusions and to determine their value as an adjunctive reverse transcription-PCR (RT-PCR) test to cytologic examination.


METHODS
One hundred fourteen serous effusions from 71 patients with tumors and 43 patients with benign diseases were subjected to RT-PCR for expression of carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (Ep-CAM), E-cadherin, mammaglobin, mucin 1 (MUC1) isoforms MUC1/REP, MUC1/Y, and MUC1/Z, calretinin, and Wilms' tumor 1 susceptibility gene.


RESULTS
CEA, Ep-CAM, E-cadherin, and mammaglobin were specifically expressed in malignant effusions. The sensitivity of RT-PCR in cytologically negative malignant effusions was 63.1% combining CEA and Ep-CAM (with 100% specificity) and reached 78.9% adding MUC1/Y or MUC1/Z (with 93% specificity). In the whole population of effusions, the combination of cytology with RT-PCR of CEA and Ep-CAM yielded a 90.1% sensitivity, a specificity and a positive predictive value of 100%, and a 86% negative predictive value for malignancy. Adding MUC1/Y or MUC1/Z to the panel, the sensitivity was 94.5% with 93% specificity, 95.7% PPV, and 90.9% negative predictive value. Moreover, CEA and mammaglobin were specifically expressed in epithelial malignancies, and mammaglobin was mainly expressed in effusions from breast carcinoma (97.3% of specificity).


CONCLUSIONS
A combination of cytology and RT-PCR analysis of CEA and Ep-CAM significantly improved the detection sensitivity of tumor cells in serous effusions. RT-PCR analysis of CEA, Ep-CAM, and mammaglobin in serous effusions could be a beneficial adjunct to cytology for the diagnosis of malignancy.
Passebosc-Faure
Karine
K
Department of Immunology, University Hospital Center, Saint Etienne, France.
Li
Guorong
G
Lambert
Claude
C
Cottier
Michèle
M
Gentil-Perret
Anne
A
Fournel
Pierre
P
Pérol
Maurice
M
Genin
Christian
C
D000368:Aged; D000941:Antigens / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D001201:Ascites / Q000378:metabolism; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000096:biosynthesis; D064032:Calbindin 2; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002277:Carcinoma / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000737:chemistry; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D016162:Genes, Wilms Tumor; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D008297:Male; D060785:Mammaglobin A; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010996:Pleural Effusion; D016066:Pleural Effusion, Malignant / Q000235:genetics* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis; D012680:Sensitivity and Specificity; D014598:Uteroglobin / Q000096:biosynthesis; D025721:WT1 Proteins / Q000096:biosynthesis
D000941:Antigens; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C576764:CALB2 protein, human; D015820:Cadherins; D064032:Calbindin 2; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D017931:DNA Primers; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; C060192:MUC1 protein, human; D060785:Mammaglobin A; D018396:Mucin-1; D009077:Mucins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D064030:S100 Calcium Binding Protein G; C556448:SCGB2A2 protein, human; D025721:WT1 Proteins; D012313:RNA; D014598:Uteroglobin