Anti‑EpCAM antibodies for detection of metastatic carcinoma in effusions and peritoneal wash

Carneiro,Fabiana  Pirani; Muniz‑Junqueira,Maria  Imaculada; Carneiro,Marcos  de Vasconcelos; Oliveira,Ísis  de Araújo; Soares,Aluízio  Carlos; Haar,Nathália  de Vargas; Takano,Gustavo  Henrique Soares; Vianna,Leonora  Maciel de Sousa; Caldas,Guilherme  de Carvalho; Vieira,Danillo  Leal Marinho; Frutuoso,Lígia  Lins; Brito,Larissa  Matos Rodrigues; de Siqueira,Rafael  Vieira Martins; Parente,Amanda  Moreira; de Castro,Tercia  Maria Mendes Lousa; Peres,Isabela; Mendes,Lianna  Martha Soares; Borges,Tatiana  Karla Dos Santos; Ferreira,Vânia   Moraes; Motoyama,Andrea  Barretto

doi:10.3892/ol.2019.10468

Anti‑EpCAM antibodies for detection of metastatic carcinoma in effusions and peritoneal wash

Authors:
- Fabiana Pirani Carneiro
- Maria Imaculada Muniz‑Junqueira
- Marcos de Vasconcelos Carneiro
- Ísis de Araújo Oliveira
- Aluízio Carlos Soares
- Nathália de Vargas Haar
- Gustavo Henrique Soares Takano
- Leonora Maciel de Sousa Vianna
- Guilherme de Carvalho Caldas
- Danillo Leal Marinho Vieira
- Lígia Lins Frutuoso
- Larissa Matos Rodrigues Brito
- Rafael Vieira Martins de Siqueira
- Amanda Moreira Parente
- Tercia Maria Mendes Lousa de Castro
- Isabela Peres
- Lianna Martha Soares Mendes
- Tatiana Karla Dos Santos Borges
- Vânia Moraes Ferreira
- Andrea Barretto Motoyama
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Affiliations: Pathological Anatomy Center of University Hospital of Brasília, Brasília 70840‑050, Brazil, Pathology Department of Brasília University, Brasília 70910‑900, Brazil, Catholic University of Brasilia, Brasília 71966‑700, Brazil
Published online on: June 12, 2019 https://doi.org/10.3892/ol.2019.10468
Pages: 2019-2024

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Abstract

Epithelial cell adhesion molecule (EpCAM) has been used as diagnostic/prognostic marker and therapeutic target. The aim of the present study was to compare immunoreactivity of antibodies against distinct epitopes in the ectodomain of EpCAM for detection of carcinoma from different primary sites and of different histological types in effusions and peritoneal wash. Two antibodies against epitopes in the EGF‑like domain I (clones Moc‑31 and Ber‑EP4) and one antibody against the epitope in the cysteine‑poor region (158210) of EpCAM were used (all commercially available). Independently of the clone used, EpCAM overexpression was observed in almost all samples when all the adenocarcinoma samples were analyzed together. By using Moc‑31, EpCAM overexpression was observed in all samples of adenocarcinoma. Absence of EpCAM overexpression was observed in a few adenocarcinoma samples at some sites of tumor origin, including ovary, breast and stomach, when Ber‑EP4 and 158210 were used. Regarding carcinomas aside from adenocarcinomas, histological types, such as squamous cell, urothelial and small cell carcinoma showed different degrees of EpCAM expression according to the antibody used. In squamous cell carcinoma, overexpression was observed only with the clone 158210. It was concluded that, overall, most samples of metastatic carcinoma from effusions showed overexpression of EpCAM. However, there are significant variations in its detection according to the primary site, histological type of the carcinoma and depending on the antibody used. Thus, the use of more than one type of anti‑EpCAM antibody would increase the chance of its detection in metastatic carcinoma effusion.

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1	Li D, Wang B, Hu Q, Shen Y, Xu D, Wang T and Wen F: Diagnostic accuracy of MOC-31 for malignant effusions: A meta-analysis. Tumour Biol. 35:6003–6009. 2014. View Article : Google Scholar : PubMed/NCBI
2	Wang B, Li D, Ou X, Yi Q and Feng Y: Diagnostic accuracy of Ber-EP4 for metastatic adenocarcinoma in serous effusions: A meta-analysis. PLoS One. 17:e1077412014. View Article : Google Scholar
3	Schnell U, Cirulli V and Giepmans BN: EpCAM: Structure and function in health and disease. Biochim Biophys Acta. 1828:1989–2001. 2013. View Article : Google Scholar : PubMed/NCBI
4	Litvinov SV, Velders MP, Bakker HA, Fleuren GJ and Warnaar SO: Ep-CAM: A human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 125:437–446. 1994. View Article : Google Scholar : PubMed/NCBI
5	Winter MJ, Nagelkerken B, Mertens AE, Rees-Bakker HA, Briaire-de Bruijn IH and Litvinov SV: Expression of EpCAM shifts the state of cadherin-mediated adhesions from strong to weak. Exp Cell Res. 285:50–58. 2003. View Article : Google Scholar : PubMed/NCBI
6	Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Münz M and Gires O: Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 11:162–171. 2009. View Article : Google Scholar : PubMed/NCBI
7	Chaves-Pérez A, Mack B, Maetzel D, Kremling H, Eggert C, Harréus U and Gires O: EpCAM regulates cell cycle progression via control of cyclin D1 expression. Oncogene. 32:641–650. 2013. View Article : Google Scholar : PubMed/NCBI
8	Du W, Ji H, Cao S, Wang L, Bai F, Liu J and Fan D: EpCAM: A potential antimetastatic target for gastric cancer. Dig Dis Sci. 55:2165–2171. 2010. View Article : Google Scholar : PubMed/NCBI
9	Baeuerle PA and Gires O: EpCAM (CD326) finding its role in cancer. Br J Cancer. 96:417–423. 2007. View Article : Google Scholar : PubMed/NCBI
10	Strand J, Hamilton AE, Beavers LS, Gamboa GC, Apelgren LD, Taber LD, Sportsman JR, Bumol TF, Sharp JD and Gadski RA: Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA. Cancer Res. 49:314–317. 1989.PubMed/NCBI
11	Winter MJ, Nagtegaal ID, van Krieken JH and Litvinov SV: The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology. Am J Pathol. 163:2139–2148. 2003. View Article : Google Scholar : PubMed/NCBI
12	Schnell U, Kuipers J and Giepmans BN: EpCAM proteolysis: New fragments with distinct functions? Biosci Rep. 33:e000302013. View Article : Google Scholar : PubMed/NCBI
13	Gastl G, Spizzo G, Obrist P, Dünser M and Mikuz G: Ep-CAM overexpression in breast cancer as a predictor of survival. Lancet. 356:1981–1982. 2000. View Article : Google Scholar : PubMed/NCBI
14	Carneiro FP, Muniz-Junqueira MI, Pittella-Silva F, Carneiro MV, Takano GHS, Vianna LMS, De Andrade LB, De Castro TMML, Peres I, Dos Santos Borges TK, et al: A panel of markers for identification of malignant and non-malignant cells in culture from effusions. Oncol Rep. 38:3538–3544. 2017.PubMed/NCBI
15	Fetsch PA, Simsir A, Brosky K and Abati A: Comparison of three commonly used cytologic preparations in effusion immunocytochemistry. Diagn Cytopathol. 26:61–66. 2002. View Article : Google Scholar : PubMed/NCBI
16	Nigro K, Tynski Z, Wasman J, Abdul-Karim F and Wang N: Comparison of cell block preparation methods for nongynecologic ThinPrep specimens. Diagn Cytopathol. 35:640–643. 2007. View Article : Google Scholar : PubMed/NCBI
17	Oda T, Ogata S, Kawaguchi S, Minabe S, Dokyu M, Takahashi H, Kumazawa F, Shimazaki H, Takano M, Hase K, et al: Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology. Diagn Cytopathol. 44:499–504. 2016. View Article : Google Scholar : PubMed/NCBI
18	Jo VY, Cibas ES and Pinkus GS: Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology. Cancer Cytopathol. 122:299–306. 2014. View Article : Google Scholar : PubMed/NCBI
19	Balzar M, Briaire-de Bruijn IH, Rees-Bakker HA, Prins FA, Helfrich W, de Leij L, Riethmuller G, Alberti S, Warnaar SO, Fleuren GJ and Litvinov SV: Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of Ep-CAM molecules in homophilic adhesions. Mol Cell Biol. 21:2570–2580. 2001. View Article : Google Scholar : PubMed/NCBI
20	Fong D, Seeber A, Terracciano L, Kasal A, Mazzoleni G, Lehne F, Gastl G and Spizzo G: Expression of EpCAM(MF) and EpCAM(MT) variants in human carcinomas. J Clin Pathol. 67:408–414. 2014. View Article : Google Scholar : PubMed/NCBI
21	Spizzo G, Fong D, Wurm M, Ensinger C, Obrist P, Hofer C, Mazzoleni G, Gastl G and Went P: EpCAM expression in primary tumour tissues and metastases: An immunohistochemical analysis. J Clin Pathol. 64:415–420. 2011. View Article : Google Scholar : PubMed/NCBI
22	Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G and Dirnhofer S: Frequent EpCam protein expression in human carcinomas. Hum Pathol. 35:122–128. 2004. View Article : Google Scholar : PubMed/NCBI
23	Pu RT, Pang Y and Michael CW: Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions. Diagn Cytopathol. 36:20–25. 2008. View Article : Google Scholar : PubMed/NCBI
24	Chantima W, Thepthai C, Cheunsuchon P and Dharakul T: EpCAM expression in squamous cell carcinoma of the uterine cervix detected by monoclonal antibody to the membrane-proximal part of EpCAM. BMC Cancer. 17:8112017. View Article : Google Scholar : PubMed/NCBI
25	Gosens MJ, van Kempen LC, van de Velde CJ, van Krieken JH and Nagtegaal ID: Loss of membranous Ep-CAM in budding colorectal carcinoma cells. Mod Pathol. 20:221–232. 2007. View Article : Google Scholar : PubMed/NCBI
26	Herreros-Pomares A, Aguilar-Gallardo C, Calabuig-Fariñas S, Sirera R, Jantus-Lewintre E and Camps C: EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale. Crit Rev Oncol Hematol. 126:52–63. 2018. View Article : Google Scholar : PubMed/NCBI