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Article / Publication Details

First-Page Preview

Received: June 26, 2022
Accepted: November 06, 2022
Published online: January 10, 2023

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 2

ISSN: 0001-5547 (Print)
eISSN: 1938-2650 (Online)

For additional information: https://www.karger.com/ACY

Abstract

Introduction: Malignant serous effusions are common in metastatic carcinomas. Although cytomorphology is recognized as the gold standard diagnostic method, it exhibits moderate sensitivity. This study aimed to assess the diagnostic value of immunophenotyping with a single epithelial marker, known as the epithelial cell adhesion molecule (EpCAM, CD326), in discriminating malignant metastatic carcinomas of serous fluids. Methods: This prospective study was conducted on suspicious or confirmed cases of malignant tumors from September 16, 2019, to June 21, 2020. Serous fluid samples were assessed via cytomorphology using the Wright-Papanicolaou method and the anti-EpCAM mouse monoclonal antibody (clone VU-1D9) flow cytometry. The EpCAM(+)/CD45(−) immunophenotype was defined as the metastatic involvement of carcinoma in the serous cavity. Results: A total of 118 samples (90 females and 28 males; mean age, 54.04 ± 16.14 years), collected from peritoneal and pleural fluids, were examined in this study. Five samples (4.24%) were positive in both EpCAM flow cytometry and cytology, while 102 samples (86.44%) were negative for both EpCAM flow cytometry and cytology, yielding an overall agreement of 92%, 84%, and 90.7% for the peritoneal, pleural, and total samples, respectively. Based on the Bayesian latent class model, the EpCAM flow cytometry showed sensitivity and specificity of 58.5% (95% CI: 0.3, 99.7) and 96.2% (95% CI: 47.8, 100), respectively. The corresponding values were 68.7% (95% CI: 0.3, 99.9) and 96.1% (95% CI: 47, 100) for cytology, respectively. Conclusion: The EpCAM flow cytometry and cytology showed comparable performance in detecting metastatic effusions. The EpCAM flow cytometry might have a diagnostic value in decreasing the false-negative rate of cytomorphology, while maintaining excellent specificity.

© 2023 S. Karger AG, Basel

References Pillai V, Cibas ES, Dorfman DM. A simplified flow cytometric immunophenotyping procedure for the diagnosis of effusions caused by epithelial malignancies. Am J Clin Pathol. 2013;139(5):672–81. Heffner JE, Klein JS. Recent advances in the diagnosis and management of malignant pleural effusions. Mayo Clin Proc. 2008;83(2):235–50. Skok K, Hladnik G, Grm A, Crnjac A. Malignant pleural effusion and its current management: a review. Medicina. 2019;55(8):490. Thomas SC, Davidson LR, McKean ME. An investigation of adequate volume for the diagnosis of malignancy in pleural fluids. Cytopathology. 2011;22(3):179–83. Abouzgheib W, Bartter T, Dagher H, Pratter M, Klump W. A prospective study of the volume of pleural fluid required for accurate diagnosis of malignant pleural effusion. Chest. 2009;135(4):999–1001. Davidson B. Malignant nonhematological effusion characterization by flow cytometry. Acta Cytol. 2016;60(4):365–71. Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood. 2008;111(8):3941–67. Chang A, Benda PM, Wood BL, Kussick SJ. Lineage-specific identification of nonhematopoietic neoplasms by flow cytometry. Am J Clin Pathol. 2003;119(5):643–55. Davidson B, Dong HP, Holth A, Berner A, Risberg B. Flow cytometric immunophenotyping of cancer cells in effusion specimens: diagnostic and research applications. Diagn Cytopathol. 2007;35(9):568–78. Kentrou NA, Tsagarakis NJ, Tzanetou K, Damala M, Papadimitriou KA, Skoumi D, et al. An improved flow cytometric assay for detection and discrimination between malignant cells and atypical mesothelial cells, in serous cavity effusions. Cytometry B Clin Cytom. 2011;80(5):324–34. Krishan A, Ganjei-Azar P, Hamelik R, Sharma D, Reis I, Nadji M. Flow immunocytochemistry of marker expression in cells from body cavity fluids. Cytometry A. 2010;77(2):132–43. Litvinov SV, Bakker HA, Gourevitch MM, Velders MP, Warnaar SO. Evidence for a role of the epithelial glycoprotein 40 (Ep-CAM) in epithelial cell-cell adhesion. Cell Adhes Commun. 1994;2(5):417–28. Balzar M, Bakker HA, Briaire-de-Bruijn IH, Fleuren GJ, Warnaar SO, Litvinov SV. Cytoplasmic tail regulates the intercellular adhesion function of the epithelial cell adhesion molecule. Mol Cell Biol. 1998;18(8):4833–43. Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, et al. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122–8. 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(7):498–504. Vos CB, Cleton-Jansen AM, Berx G, de Leeuw WJ, ter Haar NT, van Roy F, et al. E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis. Br J Cancer. 1997;76(9):1131–3. Bracke ME, Van Roy FM, Mareel MM. The E-cadherin/catenin complex in invasion and metastasis. Curr Top Microbiol Immunol. 1996;213(Pt 1):123–61. Tellechea O, Reis JP, Domingues JC, Baptista AP. Monoclonal antibody Ber EP4 distinguishes basal-cell carcinoma from squamous-cell carcinoma of the skin. Am J Dermatopathol. 1993;15(5):452–5. Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, et al. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc Natl Acad Sci U S A. 2010;107(43):18392–7. Roca E, Laroumagne S, Lacroix R, Dutau H, Judicone C, et al. False negative pleural cytology in patient with malignant pleurisies: is pleural EpCAM-positive microparticles a complementary tool for diagnosis? J Mol Biomark Diagn. 2017;8:028. Motherby H, Nadjari B, Friegel P, Kohaus J, Ramp U, Böcking A. Diagnostic accuracy of effusion cytology. Diagn Cytopathol. 1999;20(6):350–7. Oyafuso MS, Longatto Filho A, Bortolan J, Rahal P, Bisi H, Lombardo V. Cytological diagnosis of serous effusions in a cancer hospital in Brazil. Pathologica. 1996;88(2):128–31. Fetsch PA, Abati A. Immunocytochemistry in effusion cytology: a contemporary review. Cancer. 2001;93(5):293–308. Morgan RL, De Young BR, McGaughy VR, Niemann TH. MOC-31 aids in the differentiation between adenocarcinoma and reactive mesothelial cells. Cancer. 1999;87(6):390–4. 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(1):68–72. Lyons-Boudreaux V, Mody DR, Zhai J, Coffey D. Cytologic malignancy versus benignancy: how useful are the “newer” markers in body fluid cytology? Arch Pathol Lab Med. 2008;132(1):23–8. Takeshima Y, Amatya VJ, Kushitani K, Inai K. A useful antibody panel for differential diagnosis between peritoneal mesothelioma and ovarian serous carcinoma in Japanese cases. Am J Clin Pathol. 2008;130(5):771–9. Su XY, Li GD, Liu WP, Xie B, Jiang YH. Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry. Diagn Cytopathol. 2011;39(12):900–8. Patriarca C, Macchi RM, Marschner AK, Mellstedt H. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev. 2012;38(1):68–75. Sheahan K, O’Brien MJ, Burke B, Dervan PA, O'Keane JC, Gottlieb LS, et al. Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies. Am J Clin Pathol. 1990;94(2):157–64. Yu GH, Glaser LJ, Gustafson KS. Role of ancillary techniques in fluid cytology. Acta Cytol. 2020;64(1–2):52–62. Carneiro FP, Muniz-Junqueira MI, Pittella-Silva F, Carneiro MV, Takano GHS, Vianna LMS, et al. A panel of markers for identification of malignant and non-malignant cells in culture from effusions. Oncol Rep. 2017;38(6):3538–44. Darzynkiewicz Z, Halicka HD, Zhao H. Analysis of cellular DNA content by flow and laser scanning cytometry. Adv Exp Med Biol. 2010;676:137–47. Risberg B, Davidson B, Dong HP, Nesland JM, Berner A. Flow cytometric immunophenotyping of serous effusions and peritoneal washings: comparison with immunocytochemistry and morphological findings. J Clin Pathol. 2000;53(7):513–7. Yang Y, Liu YL, Shi HZ. Diagnostic accuracy of combinations of tumor markers for malignant pleural effusion: an updated meta-analysis. Respiration. 2017;94(1):62–9. Schnell U, Kuipers J, Giepmans BN. EpCAM proteolysis: new fragments with distinct functions? Biosci Rep. 2013;33(2):e00030. Article / Publication Details

First-Page Preview

Received: June 26, 2022
Accepted: November 06, 2022
Published online: January 10, 2023

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 2

ISSN: 0001-5547 (Print)
eISSN: 1938-2650 (Online)

For additional information: https://www.karger.com/ACY