Diagnostic value of CA 72‐4, carcinoembryonic antigen, CA 15‐3, and CA 19‐9 assay in pleural fluid: A study of 207 patients

BACKGROUND The differential diagnosis of pleural effusion is a frequent clinical problem. Several tumor markers have been evaluated in pleural fluid, but the value of CA 72-4 assay and of combinations of tumor marker assays has not been firmly established. To find a minimally invasive tool for differentiating between pleural effusions of malignant or benign origin, the authors assessed the diagnostic value of CA 72-4, carcinoembryonic antigen (CEA), CA 15-3, and CA 19-9 assays in pleural fluid individually and in combination. METHODS The authors prospectively studied 207 patients with pleural effusion (65 malignant, 48 tuberculous, 24 parapneumonic, 26 transudates, 14 miscellaneous, and 30 of unknown nonneoplastic origin). The levels of CA 72-4, CEA, CA 15-3, and CA 19-9 were measured in pleural fluid by radioimmunoassay. RESULTS CA 72-4 assay in pleural fluid had an acceptable sensitivity and very good specificity for diagnosing malignant pleural effusion. The combination of CA 72-4 plus CEA plus CA 15-3 yielded the best accuracy, 0.90 (95% confidence interval [CI] 0.85-0.94), with a sensitivity of 0.78 (95% CI, 0.67-0.88), specificity of 0.95 (95% CI, 0.90-0.98), positive predictive value of 0.88 (95% CI, 0.77-0.95), and negative predictive value of 0.91 (range, 0.85-0.94). A good clinical strategy may be to begin with a CEA assay (specificity of 1) and then, if it is negative, to add CA 15-3 or even CA 72-4 assays to improve sensitivity. The diagnosis of mesothelioma is more likely with a high CA 15-3 level and normal CEA and CA 19-9 levels. CONCLUSIONS Assays of CEA, CA 72-4, and CA 15-3 in pleural fluid, or the combination of CEA with CA 15-3 and CA 72-4, was useful in differentiating between pleural effusion of malignant and benign origin. Cancer 1996;78:736-40.