Diagnostic utility of CYFRA 21-1, carcinoembryonic antigen, CA 125, neuron specific enolase, and squamous cell antigen level determinations in the serum and pleural fluid of patients with pleural effusions

Cancer. 1999 Oct 15;86(8):1488-95. doi: 10.1002/(sici)1097-0142(19991015)86:8<1488::aid-cncr15>3.0.co;2-y.


Background: To the authors' knowledge the role of tumor marker determination in the differential diagnosis of pleural effusions has not been established definitively. The current article reports the results of a study of CYFRA 21-1, carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), squamous cell antigen (SCC), and neuron specific enolase (NSE) in the serum and pleural fluid of patients with pleural effusions of diverse etiologies.

Methods: One hundred forty-six patients with pleural effusions (43 malignant, 47 tuberculous, 32 miscellaneous benign, and 24 paramalignant) were studied prospectively. Levels of CYFRA 21-1, CA 125, CEA, NSE, and SCC were measured by radioimmunoassay in the pleural fluid in all patients and in the serum in 118 patients.

Results: There were no significant differences between the serum and pleural fluid levels of tumor markers with the exception of CA 125, which was higher in the pleural fluid. With maximum specificity, the highest sensitivity in the diagnosis of pleural malignancy was obtained with a combination of CYFRA 21-1 (with a cutoff value of 150 U/L), CEA (with a cutoff value of 40 ng/mL), and CA 125 (with a cutoff value of 1000 ng/mL) in pleural fluid. NSE and SCC added no diagnostic value. The simultaneous use of tumor markers and cytology in pleural fluid increased the sensitivity from 55.8% to 81%.

Conclusions: These findings suggest that a combination of CYFRA 21-1, CEA, and CA 125 in the pleural fluid can be a useful addition to pleural cytology in the diagnosis of malignant pleural effusion.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / analysis
  • Biomarkers, Tumor / analysis*
  • CA-125 Antigen / analysis
  • Carcinoembryonic Antigen / analysis
  • Exudates and Transudates / chemistry*
  • Female
  • Humans
  • Immunoradiometric Assay
  • Keratin-19
  • Keratins
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / diagnosis
  • Phosphopyruvate Hydratase / analysis
  • Pleural Effusion / blood
  • Pleural Effusion / etiology
  • Pleural Effusion / metabolism*
  • Pleural Effusion, Malignant / blood
  • Pleural Effusion, Malignant / etiology
  • Pleural Effusion, Malignant / metabolism
  • Prospective Studies
  • Serpins*
  • Tuberculosis / complications
  • Tuberculosis / diagnosis


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Carcinoembryonic Antigen
  • Keratin-19
  • Serpins
  • antigen CYFRA21.1
  • squamous cell carcinoma-related antigen
  • Keratins
  • Phosphopyruvate Hydratase