Carcinoembryonic antigen, C-reactive protein and lactate dehydrogenase measurement in pleural fluid of patients with malignant pleural effusion. A case-control study with multivariate analysis

Background: Malignant pleural effusion (MPE) is common in patients with advanced lung cancer, mesothelioma or pulmonary metastases (PMs). Unfortunately, the pleural cytology (PC) sensitivity is usually low, and thus more invasive diagnostic procedures, including video-assisted thoracoscopic (VAT)-guided biopsy, are often required. In all patients, the evaluation of specific gravity, pH, glucose and protein content of pleural fluid (PF), as well the measurement of one or pleural markers is currently performed, with the aim of confirming (or excluding) a MPE. The goal of this study was to evaluate the accuracy of PC and carcinoenbryonic antigen (CEA), C-reactive protein (CRP) and lactate dehydrogenase (LDH) assay of PF of patients with a history of cancer and a PE suspicious for metastatic disease suggesting MPE. Materials and methods: We evaluated the results of PC and PF analysis of 40 patients with confirmed MPE (cases) and 57 sex- and age-matched controls with benign pleural effusion (overall median age 71, range 28-86 years). CEA, CRP, and LDH were measured using a chemiluminescent (CLIA) immunoassay, a human sandwich (quantitative) enzyme-linked immunosorbent assay (ELISA), and a colorimetric quantification assay, respectively. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were obtained. The standard error (SE), the odds ratio (OR) and the relative 95% confidence interval (CI), and the p-value were also calculated. Results: The measurement of specific gravity, pH, glucose and protein content of PF did not differ (p=NS) between cases and controls, while pleural CEA (37.2±100-3 vs. 1.6±1.4 ng/mL, p=0.0008), CRP (5.8±8.5 vs. 11.9±7.4 mg/L, p=0.0003), and LHD (414.6±327.2 vs. 250.6±222.2 U/L, p=0.004) were significantly different. The sensitivity, specificity and accuracy of PF cytology were 45.0%, 98.2%, and 75.3%, respectively. The multivariate logistic regression analysis excluded LDH from the model and the results are reported in the Table. The AUC for the combination of PC+CEA+CRP reached 0.894 (95% CI 0.830-0.958). Conclusions: In all patients with a history of cancer and PE of uncertain origin scheduled for VAT-guided biopsy, the combination of PC and CEA+CRP measurement in the PF should be suggested.