Diagnostic value of E-cadherin and fibronectin in differentiation between reactive mesothelial and adenocarcinoma cells in serous effusions


Pathology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: One of the problems in studying serous effusion cytological samples is differentiation of reactive mesothelial cells from metastatic adenocarcinoma cells.
Materials and Methods: In this study, the immunohistochemical diagnostic value of E-cadherin and fibronectin markers for differentiation of these 2 groups of cells was studied. 50 cell block samples prepared from serous effusions were examined. Based on clinical and histological studies, 25 cases had primary carcinoma, and the other 25 were proved to be benign effusion cases. All the cases were studied for E-cadherin and fibronectin immunostaining using an envision technique. Statistical analyzes were performed employing Chi-square and exact Fisher tests, using SPSS software (version 16).
Results: 24 of the 25 benign cases were stained with fibronectin and 2 with E-cadherin, whereas from among the 25 metastatic cases, 2 reacted to fibronectin and 22 to E-cadherin. Considering the staining of the 2 markers under conditions that the cells were stained with fibronectin but not with E-cadherin, positive predictive value (PPV) and negative predictive value (NPV) to identify reactive mesothelial cells were 100% and 92.5% while under conditions that had not been stained with fibronectin but with E-cadherin, PPV and NPV to detect adenocarcinoma cells were 95.2% and 82.1%, respectively.
Conclusion: Employing this short panel can be helpful for better differentiation of adenocarcinoma and reactive mesothelial cells in serous fluids.


1. Hong EK. The Cytopathology of body cavity fluid. Korean J Cytopathol 2008;19:72-85.  Back to cited text no. 1
2. Naylor B. Pleural, peritoneal, and pericardial effusions. In: Bibbo M, editor. Comprehensive Cytopathology. 3 rd ed. Philadelphia: W.B. Saunders Elsevier; 2008. p. 515-78.  Back to cited text no. 2
3. Lisa J, Weinstein LJ, Cibas ES. Effusions (Pleural, Pericardial, and Peritoneal and Peritoneal Washing Cytopathology). In: Atkinson BF, editor. Atlas of Diagnostic Cytopathology. 2 nd ed. Saunders; 2003. p. 106-10.  Back to cited text no. 3
4. Sayed DM, el-Attar MM, Hussein AA. Evaluation of flow cytometric immunophenotyping and DNA analysis for detection of malignant cells in serosal cavity fluids. Diagn Cytopathol 2009;37:498-504.  Back to cited text no. 4
5. Fetsch PA, Abati A. Immunocytochemistry in effusion cytology. Cancer Cytopathol 2001;93:293-308.  Back to cited text no. 5
6. Rahmani A, Dehghani MZ, Afshar NM, Heidarian H, Tahririan R. HBME-1 immunostaining in reactive mesothelial versus metastatic adenocarcinoma cells in serous fluid. Indian J Pathol Microbiol 2011;54:460-3.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7. Lee JS, Nam JH, Lee MC, Park CS, Juhng SW. Immunohistochemical panel for distinguishing between carcinoma and reactive mesothelial cells in serous effusions. Acta Cytol 1996;40:631-6.  Back to cited text no. 7
8. Athanassiadou P, Gonidi M, Liossi A, Petrakakou E, Nakopoulou L, Zerva C, et al. Moc-31, fibronectin and CEA in the differential diagnosis of malignant effusions: An immunocytochemical study. Pathol Oncol Res 2000;6:100-3.  Back to cited text no. 8
9. Simsir A, Fetsch P, Mehta D, Zakowski M, Abati A. E-cadherin, N-cadherin, and calretinin in pleural effusions: The good, the bad, the worthless. Diagn Cytopathol 1999;20:125-30.  Back to cited text no. 9
10. Chhieng DC, Yee H, Cangiarella JF, Symmans WF, Cohen JM. Use of E-cadherin and CD44 aids in the differentiation between reactive mesothelial cells and carcinoma cells in pelvic washings. Cancer 2000;90:299-306.  Back to cited text no. 10
11. Gupta RK, Kenwright DN, Fauck R, Lallu S, Naran S. The usefulness of a panel of immunostains in the diagnosis and differentiation of metastatic malignancies in pericardial effusions. Cytopathology 2000;11:312-21.  Back to cited text no. 11
12. Kitazume H, Kitamura K, Mukai K, Inayama Y, Kawano N, Nakamura N, et al. Cytologic differential diagnosis among reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma: Utility of combined E-cadherin and calretinin immunostaining. Cancer 2000;90:55-60.  Back to cited text no. 12
13. Ko EC, Jhala NC, Shultz JJ, Chhieng DC. Use of a panel of markers in the differential diagnosis of adenocarcinoma and reactive mesothelial cells in fluid cytology. Am J Clin Pathol 2001;116:709-15.  Back to cited text no. 13
14. Lozano MD, Panizo A, Toledo GR, Sola JJ, Pardo-Mindán J. Immunocytochemistry in the differential diagnosis of serous effusions: A comparative evaluation of eight monoclonal antibodies in Papanicolaou stained smears. Cancer 2001;93:68-72.  Back to cited text no. 14
15. Politi E, Kandaraki C, Apostolopoulou C, Kyritsi T, Koutselini H. Immunocytochemical panel for distinguishing between carcinoma and reactive mesothelial cells in body cavity fluids. Diagn Cytopathol 2005;32:151-5.  Back to cited text no. 15
16. Malle D, Valeri RM, Photiou C, Kaplanis K, Andreadis C, Tsavdaridis D, et al. Significance of immunocytochemical expression of E-cadherin, N-cadherin and CD44 in serous effusions using liquid-based cytology. Acta Cytol 2005;49:11-6.  Back to cited text no. 16
17. Grefte JM, de Wilde PC, Salet-van de Pol MR, Tomassen M, Raaymakers-van Geloof WL, Bulten J. Improved identification of malignant cells in serous effusions using a small, robust panel of antibodies on paraffin-embedded cell suspensions. Acta Cytol 2008;52:35-44.  Back to cited text no. 17
18. Murugan P, Siddaraju N, Habeebullah S, Basu D. Immunohistochemical distinction between mesothelial and adenocarcinoma cells in serous effusions: A combination panel-based approach with a brief review of the literature. Indian J Pathol Microbiol 2009;52:175-81.  Back to cited text no. 18
[PUBMED]  Medknow Journal  
19. Metzgeroth G, Kuhn C, Schultheis B, Hehlmann R, Hastka J. Diagnostic accuracy of cytology and immunocytology in carcinomatous effusions. Cytopathology 2007;19:205-11.  Back to cited text no. 19
20. Saleh HA, El-Fakharany M, Makki H, Kadhim A, Masood S. Differentiating reactive mesothelial cells from metastatic adenocarcinoma in serous effusions: The utility of immunocytochemical panel in the differential diagnosis. Diagn Cytopathol 2009;37:324-32.  Back to cited text no. 20
21. Damsky CH, Richa J, Solter D, Knudsen K, Buck CA. Identification and purification of a cell surface glycoprotein mediating intercellular adhesion in embryonic and adult tissue. Cell 1983;34:455-66.  Back to cited text no. 21
22. Chhieng DC, Yee H, Schaefer D, Cangiarella JF, Jagirdar J, Chiriboga LA, et al. Calretinin staining pattern aids in the differentiation of mesothelioma from adenocarcinoma in serous effusions. Cancer 2000;90:194-200.  Back to cited text no. 22
23. He DN, Zhu HS, Zhang KH, Jin WJ, Zhu WM, Li N, et al. E-cadherin and calretinin as immunocytochemical markers to differentiate malignant from benign serous effusions. World J Gastroenterol 2004;10:2406-8.  Back to cited text no. 23
24. Han J, Kim MK, Nam SJ, Yang JH. E-cadherin and cytokeratin subtype profiling in effusion cytology. J Korean Med Sci 2004;19:826-33.  Back to cited text no. 24
25. Cotron RS, Kumar V, Collins T. Tissue repair: Cellular Growth, fibrosis and wound healing. Robbins pathological basis of disease. 6 th ed. WB Saunders Company; 1999. p. 89-112.  Back to cited text no. 25
26. Athanassiadou P, Athanassiades P, Lazaris D, Kyrkou K, Petrakakou E, Aravantinos D. Immunocytochemical differentiation of reactive mesothelial cells and adenocarcinoma cells in serous effusions with the use of carcinoembryonic antigen and Fibronectin. Acta Cytol 1994;38:718-22.  Back to cited text no. 26