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The Egyptian Journal of Bronchology
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Diagnostic value of calprotectin in differentiation between benign and malignant pleural effusion

Egyptian Journal of Bronchology volume 13, pages 382–387 (2019)Cite this article

Abstract

Background

Pleural effusion can arise as a result of more than 50 recognized causes and the differentiation between benign and malignant origin of the fluid is still a diagnostic challenge. The ability of tumor markers and other biological markers to make better diagnosis of malignant pleural effusion (MPE) remains questionable. Out of these, the calcium-related proteins S100-A8 and S100-A9 (the noncovalent heterodimer calprotectin) were demonstrated in a small amount in malignant not in benign pleural effusion.

Objectives

This research aimed to assess the diagnostic value of calprotectin in the differentiation between infectious or benign and MPE.

Patients and methods

Sixty patients were divided into group I: malignant and group II: infectious pleural effusions (which were further divided into group IIA: parapneumonic effusion and group IIB: tuberculous effusion) Quantitative measurement of calprotectin was done using the enzyme-linked immunosorbent assay technique in pleural effusion.

Results

Pleural calprotectin level in MPEs (229.2±168.6 ng/ ml) was significantly lower than its level of infectious pleural effusions (3202.2±1304.8 ng/ml; P<0.001). The cutoff value of calprotectin level for the diagnosis of MPE was less than or equal to 730.5 ng/ml, with 95% confidence interval and the area under the curve was 0.999, the corresponding sensitivity was 96.7 and the specificity was 100% (P<0.001).

Conclusion

Calprotectin is a valuable biomarker in differentiating malignant from infectious pleural effusion.

References

  1. Mohamed SA, Agmy GR, Wafy SA, Abd El-Hameed MG. Value of C-reactive protein in differentiation between tuberculous and malignant pleural effusion. Egypt J Bronchol 2017; 11:49–55.

    Article  Google Scholar 

  2. Neragi-Miandoab S. Malignant pleural effusion, current and evolving approaches for its diagnosis and management. Lung Cancer 2006; 54:1–9.

    Article  Google Scholar 

  3. Hooper C, Lee YC, Maskell N. Investigation of unilateral pleural effusion in adults:British Thoracic Society Pleural Disease Guideline. Thorax 2010; 65 (Suppl 2):ii4–ii17.

    Article  Google Scholar 

  4. Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ. Management of malignant pleural effusion:British Thoracic Society Pleural Disease Guideline 2010. Thorax 2010; 65:ii32–ii40.

  5. Botana-Rial M, Casado-Rey P, Leiro-Fernandez V, Andrade-Olivie M, Represas-Represas C, Fernandez-Villar A. Validity of procalcitonin and C-reactive protein measurement when differentiating between benign and malignant pleural effusion. Clin Lab 2011; 57:373–378.

    CAS  Google Scholar 

  6. Rodrıguez-Pineiro AM, Blanco-Prieto S, Sanchez-Otero N, Rodrıguez-Berrocal FJ, de la Cadena MP. On the identification of biomarkers for non-small cell lung cancer in serum and pleural effusion. J Proteomics 2010; 73:1511–1522.

    Article  Google Scholar 

  7. Vermeire S, Van Assche G, Rutgeerts P. Laboratory markers in IBD:useful, magic, or unnecessary toys? Gut 2006; 55:426–431.

  8. Fagerhol MK, Dale I, Andersson T. Release and quantitation of a leukocyte derived protein L1. Scan J Haematol 1980; 24:393–398.

    CAS  Google Scholar 

  9. Ghavami S, Chitayat S, Hashemi M, Eshraghi M, Chazin WJ, Halayko AJ, et al. S100A8/A9:a Janus-faced molecule in cancer therapy and tumorigenesis. Eur J Pharmacol 2009; 625:73–83.

    Article  CAS  Google Scholar 

  10. Odegaard E, Davidson B, Engh V, Onsrud M, Staff AC. Assessment of endoglin and calprotectin as potential biomarkers in ovarian carcinoma and borderline tumors of the ovary. Obstet Gynecol 2008; 199:533.el–8.

    Google Scholar 

  11. Hermann A, Hess J, De Servi B, Medunjanin S, Grobholz R, Trojan L, et al. Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res 2005; 11:5146–5152.

    Article  Google Scholar 

  12. Kremer R, Best LA, Savulescu D, Gavish M, Nagler RM. Pleural fluid analysis of lung cancer vs. benign inflammatory disease patients. Br J Cancer 2010; 102:1180–1184.

    CAS  PubMed  Google Scholar 

  13. Zhang W, Yang HC, Wang Q, Yang ZJ, Chen H, Wang SM, et al. Clinical value of combined detection of serum matrix metalloproteinase-9, heparanase, and cathepsin for determining ovarian cancer invasion and metastasis. Anticancer Res 2011; 31:3423–3428.

    CAS  PubMed  Google Scholar 

  14. Srikrishna G, Panneerselvam K, Westphal V. Two proteins modulating transendothelial migration of leukocytes recognize novel carboxylated glycans on endothelial cells. J Immunol 2001; 166:4678–4688.

    Article  CAS  Google Scholar 

  15. Kallel L, Fekih M, Boubaker J, Filali A. Faecal calprotectin in inflammatory bowel diseases:a review. Tunis Med 2011; 89:425–429.

    PubMed  Google Scholar 

  16. Gebhardt C, Nemeth J, Angel P, Hess J. S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol 2006; 72:1622–1631.

    Article  CAS  Google Scholar 

  17. Nisapakultorn K, Ross KF, Herzberg MC. Calprotectin expression inhibits bacterial binding to mucosal epithelial cells. Infect Immun 2001; 69:3692–3696.

    Article  CAS  Google Scholar 

  18. Sanchez-Otero N, Blanco-Prieto S, Paez de la Cadena M, Vázquez-Iglesias L, Fernández-Villar A, Botana-Rial MI, et al. Calprotectin:a novel biomarker for the diagnosis of pleural effusion. Br J Cancer 2012; 107:1876–1882.

    Article  CAS  Google Scholar 

  19. Xuan W, Zhang J, Zhou Q, Ma LJ. Role of interleukin –33 in the differentiation between tuberculous and malignant pleural effusion. Oncol Lett 2014; 8:449–453.

    Article  CAS  Google Scholar 

  20. Light RW. Pleural diseases. 4th ed. Philadelphia, PA:Lippincott Williams, and Wilkins; 2001. 392–394

    Google Scholar 

  21. Kothari CR. Research methodology:methods and techniques. 2nd ed. New Delhi:New Age International Publishers; 2004.

    Google Scholar 

  22. Luo J, Wang M, Li C, Liang B, Liu D, Shi C, et al. A novel combination of calprotectin and CXCL12 for predicting malignancy in patients with exudative pleural effusion. Medicine (Baltimore) 2015; 94:e2105.

  23. Kohmo S, Kijima T, Mori M, Minami T, Namba Y, Yano Y, et al. CXCL12 as a biological marker for the diagnosis of tuberculous pleurisy. Tuberculosis 2012; 92:248–252.

    Article  CAS  Google Scholar 

  24. Su YJ, Xu F, Yu JP, Yue DS, Ren XB, Wang CL. Up-regulation of the expression of S100A8 and S100A9 in lung adenocarcinoma and its correlation with inflammation and other clinical features. Chin Med J 2010; 123:2215–2220.

    CAS  PubMed  Google Scholar 

  25. Blanco-Prieto S, Vázquez-Iglesias L, Rodriguez-Girondo M, Barcia-Castro L, Femández-Villar A, Botana-Rial MI, et al. Serum calprotectin, CD26 and EGF to establish a panel for the diagnosis of lung cancer. PloS ONE 2015; 10:e0127318.

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Authors and Affiliations

  1. Department of Chest Diseases, Faculty of Medicine, Benha University, Benha, Qalyubia, 13511, Egypt

    Omar M. Mohammed, Kamel M. Hussein, Gouda T. Mahmoud, Marwa El-Sayed El-Naggar MD & Nor Eldein Z. Gaber

  2. Department of Clinical Pathology, Faculty of Medicine, Benha University, Benha, Egypt

    Abdelgawad E. Ramadan

Authors
  1. Omar M. Mohammed
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  2. Kamel M. Hussein
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  3. Abdelgawad E. Ramadan
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  4. Gouda T. Mahmoud
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  5. Marwa El-Sayed El-Naggar MD
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  6. Nor Eldein Z. Gaber
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Corresponding author

Correspondence to Marwa El-Sayed El-Naggar MD.

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Mohammed, O.M., Hussein, K.M., Ramadan, A.E. et al. Diagnostic value of calprotectin in differentiation between benign and malignant pleural effusion. Egypt J Bronchol 13, 382–387 (2019). https://doi.org/10.4103/ejb.ejb_77_18

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  • DOI: https://doi.org/10.4103/ejb.ejb_77_18

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