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Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

EpCAM expression in squamous cell carcinoma of the uterine cervix detected by monoclonal antibody to the membrane-proximal part of EpCAM

Authors: Warangkana Chantima, Charin Thepthai, Pornsuk Cheunsuchon, Tararaj Dharakul

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Epithelial cell adhesion molecule (EpCAM) is a promising biomarker for squamous cell carcinoma (SCC) of the uterine cervix, because it is over-expressed in various cancers of epithelial origin. However, EpCAM expression reported in previous immunohistochemistry (IHC) studies was inconsistent. We hypothesize that the membrane-distal part of EpCAM may be lost during tissue preparation, leaving only the membrane-proximal part of EpCAM available for antibody binding and IHC staining.

Methods

Two new anti-EpCAM MAbs to the membrane-proximal part (WC-2) and the membrane-distal part (WC-1) of EpCAM were generated and characterized. WC-2 was selected for its ability to detect EpCAM in cervical tissues by IHC. One hundred thirty-five archival paraffin-embedded tissues previously diagnosed as cervical SCC (n=44), high-grade (HSIL) (n=43), or low-grade (LSIL) (n=48) squamous intraepithelial lesions were examined. IHC score was collected, recorded, and analyzed for distribution, intensity, and percentage of cancer cells stained for EpCAM.

Results

EpCAM expression was consistently detected on cervical tissues by WC-2, but not by WC-1. EpCAM was expressed with high IHC score in the majority of cervical SCC (37/44), but not in normal epithelial area adjacent to SCC. EpCAM was also highly expressed on precancerous lesion of the cervix, particularly in HSIL. More importantly, EpCAM expression could be used to distinguish between HSIL and LSIL, according to staining distribution. HSIL tissues displayed EpCAM expression in two-thirds to full thickness of the epithelium, while in LSIL the staining was limited to the lower one-third of the thickness. The IHC score of EpCAM expression was strongly correlated with cervical cancer and grades of precancerous lesions (r=0.875, p<0.001).

Conclusion

Only the anti-EpCAM MAb to the membrane-proximal part is able to detect EpCAM on paraffin-embedded cervical cancer tissues. A strong positive correlation between EpCAM expression level and the grades of SILs provides the possibility that EpCAM can be used to predict prognosis and severity in these patients.
Literature
1.
go back to reference Chao A, Wang TH, Lee YS, Hsueh S, Chao AS, Chang TC, Kung WH, Huang SL, Chao FY, Wei ML, et al. Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression. Int J Cancer. 2006;119(1):91–8.CrossRefPubMed Chao A, Wang TH, Lee YS, Hsueh S, Chao AS, Chang TC, Kung WH, Huang SL, Chao FY, Wei ML, et al. Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression. Int J Cancer. 2006;119(1):91–8.CrossRefPubMed
2.
go back to reference Imadome K, Iwakawa M, Nakawatari M, Fujita H, Kato S, Ohno T, Nakamura E, Ohkubo Y, Tamaki T, Kiyohara H, et al. Subtypes of cervical adenosquamous carcinomas classified by EpCAM expression related to radiosensitivity. Cancer Biol Ther. 2010;10(10):1019–26.CrossRefPubMed Imadome K, Iwakawa M, Nakawatari M, Fujita H, Kato S, Ohno T, Nakamura E, Ohkubo Y, Tamaki T, Kiyohara H, et al. Subtypes of cervical adenosquamous carcinomas classified by EpCAM expression related to radiosensitivity. Cancer Biol Ther. 2010;10(10):1019–26.CrossRefPubMed
3.
go back to reference Spizzo G, Fong D, Wurm M, Ensinger C, Obrist P, Hofer C, Mazzoleni G, Gastl G, Went P. EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. J Clin Pathol. 2011;64(5):415–20.CrossRefPubMedPubMedCentral Spizzo G, Fong D, Wurm M, Ensinger C, Obrist P, Hofer C, Mazzoleni G, Gastl G, Went P. EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. J Clin Pathol. 2011;64(5):415–20.CrossRefPubMedPubMedCentral
4.
go back to reference Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, Dirnhofer S. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122–8.CrossRefPubMed Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, Dirnhofer S. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35(1):122–8.CrossRefPubMed
5.
go back to reference Litvinov SV, van Driel W, van Rhijn CM, Bakker HA, van Krieken H, Fleuren GJ, Warnaar SO. Expression of ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation. Am J Pathol. 1996;148(3):865–75.PubMedPubMedCentral Litvinov SV, van Driel W, van Rhijn CM, Bakker HA, van Krieken H, Fleuren GJ, Warnaar SO. Expression of ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation. Am J Pathol. 1996;148(3):865–75.PubMedPubMedCentral
6.
go back to reference Edwards DP, Grzyb KT, Dressler LG, Mansel RE, Zava DT, Sledge GW, Jr., McGuire WL. Monoclonal antibody identification and characterization of a Mr 43,000 membrane glycoprotein associated with human breast cancer. Cancer Res 1986;46(3):1306–1317. Edwards DP, Grzyb KT, Dressler LG, Mansel RE, Zava DT, Sledge GW, Jr., McGuire WL. Monoclonal antibody identification and characterization of a Mr 43,000 membrane glycoprotein associated with human breast cancer. Cancer Res 1986;46(3):1306–1317.
7.
go back to reference Schnell U, Cirulli V, Giepmans BNG. EpCAM. Structure and function in health and disease. Biochim Biophys Acta. 2013;1828(8):1989–2001.CrossRefPubMed Schnell U, Cirulli V, Giepmans BNG. EpCAM. Structure and function in health and disease. Biochim Biophys Acta. 2013;1828(8):1989–2001.CrossRefPubMed
8.
go back to reference Schnell U, Kuipers J, Giepmans BNG. EpCAM proteolysis: new fragments with distinct functions? Biosci Rep. 2013;33:321–U426.CrossRef Schnell U, Kuipers J, Giepmans BNG. EpCAM proteolysis: new fragments with distinct functions? Biosci Rep. 2013;33:321–U426.CrossRef
9.
go back to reference Balzar M, Briaire-de Bruijn IH, Rees-Bakker HA, Prins FA, Helfrich W, de Leij L, Riethmuller G, Alberti S, Warnaar SO, Fleuren GJ, et al. Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of ep-CAM molecules in homophilic adhesions. Mol Cell Biol. 2001;21(7):2570–80.CrossRefPubMedPubMedCentral Balzar M, Briaire-de Bruijn IH, Rees-Bakker HA, Prins FA, Helfrich W, de Leij L, Riethmuller G, Alberti S, Warnaar SO, Fleuren GJ, et al. Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of ep-CAM molecules in homophilic adhesions. Mol Cell Biol. 2001;21(7):2570–80.CrossRefPubMedPubMedCentral
10.
go back to reference Balzar M, Winter MJ, de Boer CJ, Litvinov SV. The biology of the 17-1A antigen (ep-CAM). J Mol Med (Berl). 1999;77(10):699–712.CrossRef Balzar M, Winter MJ, de Boer CJ, Litvinov SV. The biology of the 17-1A antigen (ep-CAM). J Mol Med (Berl). 1999;77(10):699–712.CrossRef
11.
go back to reference Winter MJ, Nagtegaal ID, van Krieken JH, Litvinov SV. The epithelial cell adhesion molecule (ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology. Am J Pathol. 2003;163(6):2139–48.CrossRefPubMedPubMedCentral Winter MJ, Nagtegaal ID, van Krieken JH, Litvinov SV. The epithelial cell adhesion molecule (ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology. Am J Pathol. 2003;163(6):2139–48.CrossRefPubMedPubMedCentral
12.
go back to reference Helfrich W, Koning PW. The TH, de Leij L. epitope mapping of SCLC-cluster-2 MAbs and generation of antibodies directed against new EGP-2 epitopes. Int J Cancer Suppl. 1994;8:64–9.CrossRefPubMed Helfrich W, Koning PW. The TH, de Leij L. epitope mapping of SCLC-cluster-2 MAbs and generation of antibodies directed against new EGP-2 epitopes. Int J Cancer Suppl. 1994;8:64–9.CrossRefPubMed
13.
go back to reference Fornaro M, Dell'Arciprete R, Stella M, Bucci C, Nutini M, Capri MG, Alberti S. Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas. Int J Cancer. 1995;62(5):610–8.CrossRefPubMed Fornaro M, Dell'Arciprete R, Stella M, Bucci C, Nutini M, Capri MG, Alberti S. Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas. Int J Cancer. 1995;62(5):610–8.CrossRefPubMed
14.
go back to reference Wentzensen N, Fetterman B, Castle PE, Schiffman M, Wood SN, Stiemerling E, Tokugawa D, Bodelon C, Poitras N, Lorey T et al. p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women. J Natl Cancer Inst. 2015;107(12):djv257. Wentzensen N, Fetterman B, Castle PE, Schiffman M, Wood SN, Stiemerling E, Tokugawa D, Bodelon C, Poitras N, Lorey T et al. p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women. J Natl Cancer Inst. 2015;107(12):djv257.
15.
go back to reference Ikenberg H, Bergeron C, Schmidt D, Griesser H, Alameda F, Angeloni C, Bogers J, Dachez R, Denton K, Hariri J, et al. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst. 2013;105(20):1550–7.CrossRefPubMedPubMedCentral Ikenberg H, Bergeron C, Schmidt D, Griesser H, Alameda F, Angeloni C, Bogers J, Dachez R, Denton K, Hariri J, et al. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst. 2013;105(20):1550–7.CrossRefPubMedPubMedCentral
16.
go back to reference Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011;6(9):1083–98.CrossRefPubMed Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011;6(9):1083–98.CrossRefPubMed
17.
go back to reference Chen JS, Lan K, Hung MC. Strategies to target HER2/neu overexpression for cancer therapy. Drug Resist Updat. 2003;6(3):129–36.CrossRefPubMed Chen JS, Lan K, Hung MC. Strategies to target HER2/neu overexpression for cancer therapy. Drug Resist Updat. 2003;6(3):129–36.CrossRefPubMed
18.
go back to reference Emens LA. Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. Am J Ther. 2005;12(3):243–53.PubMed Emens LA. Trastuzumab: targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. Am J Ther. 2005;12(3):243–53.PubMed
19.
go back to reference Markman JL, Shiao SL. Impact of the immune system and immunotherapy in colorectal cancer. J Gastrointest Oncol. 2015;6(2):208–23.PubMedPubMedCentral Markman JL, Shiao SL. Impact of the immune system and immunotherapy in colorectal cancer. J Gastrointest Oncol. 2015;6(2):208–23.PubMedPubMedCentral
20.
go back to reference Xiang B, Snook AE, Magee MS, Waldman SA. Colorectal cancer immunotherapy. Discov Med. 2014;15(84):301–8. Xiang B, Snook AE, Magee MS, Waldman SA. Colorectal cancer immunotherapy. Discov Med. 2014;15(84):301–8.
21.
go back to reference Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, Solomon D, Wentzensen N, Lawson HW. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):829–46.CrossRefPubMed Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, Solomon D, Wentzensen N, Lawson HW. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013;121(4):829–46.CrossRefPubMed
Metadata
Title
EpCAM expression in squamous cell carcinoma of the uterine cervix detected by monoclonal antibody to the membrane-proximal part of EpCAM
Authors
Warangkana Chantima
Charin Thepthai
Pornsuk Cheunsuchon
Tararaj Dharakul
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3798-z

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