Skip to main content

Advertisement

Log in

Diagnostic accuracy of tumour markers in serous effusions: a validation study

  • Research Article
  • Published:
Tumor Biology

Abstract

The utility of tumour markers (TM) in the differential diagnosis of cancer in serous effusion (fluid effusion (FE)) has been the subject of controversy. The aim of this study was to prospectively validate our previous study and to assess whether the addition of adenosine deaminase (ADA), C-reactive protein (CRP) or percentage of polymorphonuclear cells (%PN) allows the identification of false positives. In this study, carcinoembryonic antigen, cancer antigen 15-3, cancer antigen 19-9, ADA, CRP and %PN in FE were determined in 347 patients with 391 effusions. Effusions were considered as malignant effusion when at least one TM in serum exceeded the cutoff and the ratio FE/S was higher than 1.2. Also, cases with values of ADA, CRP and %PN above the established cutoffs in serous effusion were considered as potential false positives. The combined sensitivity and specificity of the three TM was 76.2 % (95 % confidence intervals (CI) 67.8–83.3 %) and 97.0 % (95 % CI 94.1–98.7), respectively. Subanalysis of the 318 cases with previous criteria and negative ADA, CRP and %PN obtained sensitivities of 78.4 % (95 % CI 69.4–85.6) and a specificity of 100 % (95 % CI 98.2–100). The results obtained validate our previous study and are improved with the addition of ADA, CRP and %PN. TM in serous effusions and serum could be useful for the diagnostic assessment of patients with serous effusions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ADA:

Adenosine deaminase

CA125:

Cancer antigen 125

CA15-3:

Cancer antigen 15-3

CA19-9:

Cancer antigen 19-9

CEA:

Carcinoembryonic antigen

CI:

Confidence intervals

CRP:

C-reactive protein

CYFRA 21-1:

Cytokeratin 19 fragment

FE:

Fluid effusion

NPV:

Negative predictive value

PPV:

Positive predictive value

NLH:

Negative likelihood ratio

PLH:

Positive likelihood ratio

%PN:

Percentage of polymorphonuclear cells

S:

Serum

TM:

Tumour markers

References

  1. Light RW. Clinical practice. Pleural effusion. N Engl J Med. 2002;346:1971–7.

    Article  PubMed  Google Scholar 

  2. Runyon BA. Care of patients with ascites. N Engl J Med. 1994;330:337–42.

    Article  CAS  PubMed  Google Scholar 

  3. Fenton KN, Richardson JD. Diagnosis and management of malignant pleural effusions. Am J Surg. 1995;170:69–74.

    Article  CAS  PubMed  Google Scholar 

  4. Miédougé M, Rouzaud P, Salama G, et al. Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions. Br J Cancer. 1999;81:1059–61.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gulyás M, Kaposi AD, Elek G, et al. Value of carcinoembryonic (CEA) and cholesterol assays of ascitic fluid in cases of inconclusive cytology. J Clin Pathol. 2001;54:831–5.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Satoh H, Sumi M, Yagyu H, et al. Clinical evaluation of CYFRA 21-1 in malignant pleural fluids. Oncology. 1995;52:211–4.

    Article  CAS  PubMed  Google Scholar 

  7. Romero S, Fernández C, Arriero JM, et al. CEA, CA 15-3 and CYFRA 21-1 in serum and pleural fluid of patients with pleural effusions. Eur Respir J. 1996;9:17–23.

    Article  CAS  PubMed  Google Scholar 

  8. Lee JH, Chang JH. Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments in patients with effusions from primary lung cancer. Chest. 2005;128(4):2298–303.

    Article  PubMed  Google Scholar 

  9. Ferroni P, Szpak C, Greiner JW, et al. CA 72-4 radioimmunoassay in the diagnosis of malignant effusions. Comparison of various tumor markers. Int J Cancer. 1990;46(3):445–51.

    Article  CAS  PubMed  Google Scholar 

  10. Marel M, Stastny B, Melínová L, et al. Diagnosis of pleural effusions. Experience with clinical studies, 1986 to 1990. Chest. 1995;107(6):1598–603.

    Article  CAS  PubMed  Google Scholar 

  11. Garcia-Pachon E, Padilla-Navas I, Dosada D, et al. Elevated levels of carcinoembryonic antigen in nonmalignant pleural effusions. Chest. 1997;111(3):643–7.

    Article  CAS  PubMed  Google Scholar 

  12. Ferrer J, Villarino MA, Encabo G, et al. 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;86(8):1488–95.

    Article  CAS  PubMed  Google Scholar 

  13. San Jose ME, Alvarez D, Valdes L, et al. Utility of tumour markers in the diagnosis of neoplastic pleural effusion. Clin Chim Acta. 1997;265:193–205.

    Article  CAS  PubMed  Google Scholar 

  14. Villena V, López-Encuentra A, Echave-Sustaeta J, et al. Diagnostic value of CA 72-4, carcinoembryonic antigen, CA 15-3, and CA 19-9 assay in pleural fluid. A study of 207 patients. Cancer. 1996;78:736–40.

    Article  CAS  PubMed  Google Scholar 

  15. Hernandez L, Espasa A, Fernandez C, et al. CEA and CA 549 in serum and pleural fluid of patients with pleural effusion. Lung Cancer. 2002;36:83–9.

    Article  PubMed  Google Scholar 

  16. Porcel JM, Vives M, Esquerda A, et al. Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions. Chest. 2004;126:1757–63.

    Article  PubMed  Google Scholar 

  17. Trapé J, Filella X, Alsina-Donadeu M, et al. Increased plasma concentrations of tumour markers in the absence of neoplasia. Clin Chem Lab Med. 2011;49:1605–20.

    Article  PubMed  Google Scholar 

  18. Cases A, Filella X, Molina R, et al. Tumor markers in chronic renal failure and hemodialysis patients. Nephron. 1991;57:183–6.

    Article  CAS  PubMed  Google Scholar 

  19. Trape J, Molina R, Sant F. Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions. Tumour Biol. 2004;25:276–81.

    Article  CAS  PubMed  Google Scholar 

  20. Segura RM, Pascual C, Ocana I, et al. Adenosine deaminase in body fluids: a useful diagnostic tool in tuberculosis. Clin Biochem. 1989;22:141–8.

    Article  CAS  PubMed  Google Scholar 

  21. Castaño Vidriales JL, Amores Antequera C. Use of pleural fluid C-reactive protein in laboratory diagnosis of pleural effusions. Eur J Med. 1992;1:201–7.

    PubMed  Google Scholar 

  22. Garcia-Pachon E, Soler MJ, Padilla-Navas I, et al. C-reactive protein in lymphocytic pleural effusions: a diagnostic aid in tuberculous pleuritis. Respiration. 2005;72:486–9.

    Article  CAS  PubMed  Google Scholar 

  23. Chierakul N, Kanitsap A, Chaiprasert A, et al. A simple C-reactive protein measurement for the differentiation between tuberculous and malignant pleural effusion. Respirology. 2004;9:66–9.

    Article  PubMed  Google Scholar 

  24. Chen SC, Chen W, Hsu WH, et al. Role of pleural fluid C-reactive protein concentration in discriminating uncomplicated parapneumonic pleural effusions from complicated parapneumonic effusion and empyema. Lung. 2006;184:141–5.

    Article  CAS  PubMed  Google Scholar 

  25. Garcia-Pachon E, Llorca I. Diagnostic value of C-reactive protein in exudative pleural effusions. Eur J Intern Med. 2002;13:246–9.

    Article  CAS  PubMed  Google Scholar 

  26. Tahhan M, Ugurman F, Gozu A, et al. Tumour necrosis factor-alpha in comparison to adenosine deaminase in tuberculous pleuritis. Respiration. 2003;70:270–4.

    Article  CAS  PubMed  Google Scholar 

  27. Deeks JJ, Altman DG. Diagnostic tests 4: likelihood ratios. BMJ. 2004;329(7458):168–9.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Light RW. Tumor markers in undiagnosed pleural effusions. Chest. 2004;126:1721–2.

    Article  PubMed  Google Scholar 

  29. Buffet C, Fourre C, Altman C, et al. Bile levels of carcino-embryonic antigen in patients with hepatopancreatobiliary disease. Eur J Gastroenterol Hepatol. 1996;8:131–4.

    Article  CAS  PubMed  Google Scholar 

  30. Akdogan M, Parlak E, Kayhan B, et al. Are serum and biliary carcinoembryonic antigen and carbohydrate antigen19-9 determinations reliable for differentiation between benign and malignant biliary disease? Turk J Gastroenterol. 2003;14:181–4.

    PubMed  Google Scholar 

  31. Ferrer J, Roldán J, Teixidor J, et al. Predictors of pleural malignancy in patients with pleural effusion undergoing thoracoscopy. Chest. 2005;127:1017–22.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study has been awarded the XIII prize of Bages de Ciències Mèdiques 2009, granted by the Fundació Acadèmia de Ciències Mèdiques de Catalunya i Balears, Bages branch. The authors also thank Sylva Astrik Torossian for the support to the manuscript edition and translation.

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jaume Trapé.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trapé, J., Molina, R., Sant, F. et al. Diagnostic accuracy of tumour markers in serous effusions: a validation study. Tumor Biol. 33, 1661–1668 (2012). https://doi.org/10.1007/s13277-012-0422-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0422-3

Keywords

Navigation