Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker

Authors: Nikolas H Stoecklein, Annika Siegmund, Peter Scheunemann, Andreas M Luebke, Andreas Erbersdobler, Pablo E Verde, Claus F Eisenberger, Matthias Peiper, Alexander Rehders, Jan Schulte am Esch, Wolfram Trudo Knoefel, Stefan B Hosch

Published in: BMC Cancer | Issue 1/2006

Login to get access

Abstract

Background

To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies.

Methods

The Ep-CAM expression was immunohistochemically investigated in 70 primary esophageal SCCs using the monoclonal antibody Ber-EP4. For the interpretation of the staining results, we used a standardized scoring system ranging from 0 to 3+. The survival analysis was calculated from 53 patients without distant metastasis, with R0 resection and at least 2 months of clinical follow-up.

Results

Ep-CAM neo-expression was observed in 79% of the tumors with three expression levels, 1+ (26%), 2+ (11%) and 3+ (41%). Heterogeneous expression was observed at all expression levels. Interestingly, tumors with 3+ Ep-CAM expression conferred a significantly decreased median relapse-free survival period (log rank, p = 0.0001) and median overall survival (log rank, p = 0.0003). Multivariate survival analysis disclosed Ep-CAM 3+ expression as independent prognostic factor.

Conclusion

Our results suggest Ep-CAM as an attractive molecule for targeted therapy in esophageal SCC. Considering the discontenting results of the current adjuvant concepts for esophageal SCC patients, Ep-CAM might provide a promising target for an adjuvant immunotherapeutic intervention.
Appendix
Available only for authorised users
Literature
1.
Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med. 2003, 349 (23): 2241-2252. 10.1056/NEJMra035010.CrossRefPubMed
2.
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ: Cancer statistics, 2005. CA Cancer J Clin. 2005, 55 (1): 10-30.CrossRefPubMed
3.
Greer SE, Goodney PP, Sutton JE, Birkmeyer JD: Neoadjuvant chemoradiotherapy for esophageal carcinoma: a meta-analysis. Surgery. 2005, 137 (2): 172-177. 10.1016/j.surg.2004.06.033.CrossRefPubMed
4.
Malthaner RA, Wong RK, Rumble RB, Zuraw L: Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a clinical practice guideline. BMC Cancer. 2004, 4 (1): 67-10.1186/1471-2407-4-67.CrossRefPubMedPubMedCentral
5.
Malthaner RA, Wong RK, Rumble RB, Zuraw L: Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis. BMC Med. 2004, 2 (1): 35-10.1186/1741-7015-2-35.CrossRefPubMedPubMedCentral
6.
Linnenbach AJ, Pressler LB, Seng BA, Kimmel BS, Tomaszewski JE, Malkowicz SB: Characterization of chromosome 9 deletions in transitional cell carcinoma by microsatellite assay. Hum Mol Genet. 1993, 2 (9): 1407-1411.CrossRefPubMed
7.
Spurr NK, Durbin H, Sheer D, Parkar M, Bobrow L, Bodmer WF: Characterization and chromosomal assignment of a human cell surface antigen defined by the monoclonal antibody AUAI. Int J Cancer. 1986, 38 (5): 631-636.CrossRefPubMed
8.
Calabrese G, Crescenzi C, Morizio E, Palka G, Guerra E, Alberti S: Assignment of TACSTD1 (alias TROP1, M4S1) to human chromosome 2p21 and refinement of mapping of TACSTD2 (alias TROP2, M1S1) to human chromosome 1p32 by in situ hybridization. Cytogenet Cell Genet. 2001, 92 (1-2): 164-165. 10.1159/000056891.CrossRefPubMed
9.
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): 417-428.CrossRefPubMed
10.
Litvinov SV, Balzar M, Winter MJ, Bakker HA, Briaire-de Bruijn IH, Prins F, Fleuren GJ, Warnaar SO: Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins. J Cell Biol. 1997, 139 (5): 1337-1348. 10.1083/jcb.139.5.1337.CrossRefPubMedPubMedCentral
11.
Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO: Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 1994, 125 (2): 437-446. 10.1083/jcb.125.2.437.CrossRefPubMed
12.
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): 4833-4843.CrossRefPubMedPubMedCentral
13.
Balzar M, Winter MJ, de Boer CJ, Litvinov SV: The biology of the 17-1A antigen (Ep-CAM). J Mol Med. 1999, 77 (10): 699-712. 10.1007/s001099900038.CrossRefPubMed
14.
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): 2139-2148.CrossRefPubMedPubMedCentral
15.
Gastl G, Spizzo G, Obrist P, Dunser M, Mikuz G: Ep-CAM overexpression in breast cancer as a predictor of survival. Lancet. 2000, 356 (9246): 1981-1982. 10.1016/S0140-6736(00)03312-2.CrossRefPubMed
16.
Spizzo G, Went P, Dirnhofer S, Obrist P, Simon R, Spichtin H, Maurer R, Metzger U, von Castelberg B, Bart R, Stopatschinskaya S, Kochli OR, Haas P, Mross F, Zuber M, Dietrich H, Bischoff S, Mirlacher M, Sauter G, Gastl G: High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res Treat. 2004, 86 (3): 207-213. 10.1023/B:BREA.0000036787.59816.01.CrossRefPubMed
17.
Varga M, Obrist P, Schneeberger S, Muhlmann G, Felgel-Farnholz C, Fong D, Zitt M, Brunhuber T, Schafer G, Gastl G, Spizzo G: Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival. Clin Cancer Res. 2004, 10 (9): 3131-3136. 10.1158/1078-0432.CCR-03-0528.CrossRefPubMed
18.
Armstrong A, Eck SL: EpCAM: A new therapeutic target for an old cancer antigen. Cancer Biol Ther. 2003, 2 (4): 320-326.CrossRefPubMed
19.
Heiss MM, Strohlein MA, Jager M, Kimmig R, Burges A, Schoberth A, Jauch KW, Schildberg FW, Lindhofer H: Immunotherapy of malignant ascites with trifunctional antibodies. Int J Cancer. 2005, 117 (3): 435-443. 10.1002/ijc.21165.CrossRefPubMed
20.
Schmitt M, Schmitt A, Reinhardt P, Thess B, Manfras B, Lindhofer H, Riechelmann H, Wiesneth M, Gronau S: Opsonization with a trifunctional bispecific (alphaCD3 x alphaEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes. Int J Oncol. 2004, 25 (4): 841-848.PubMed
21.
Stemmler HJ, Salat C, Lindhofer H, Menzel H, Untch M, Kahlert S, Konecny G, Sauer H, Ledderose G, Heinemann V, Kolb HJ: Combined treatment of metastatic breast cancer (MBC) by high-dose chemotherapy (HDCT) and bispecific antibodies: a pilot study. Anticancer Res. 2005, 25 (4): 3047-3054.PubMed
22.
UICC - TNM Classification of Malignant Tumours. Edited by: Sobin LH, Wittekind C. 1997, New York , Wiley-Liss, 5th
23.
Hosch SB, Stoecklein NH, Pichlmeier U, Rehders A, Scheunemann P, Niendorf A, Knoefel WT, Izbicki JR: Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance. J Clin Oncol. 2001, 19 (7): 1970-1975.PubMed
24.
Schwarz G: Estimating the dimension of a model. Annals of Statistics. 1978, 6: 461-464.CrossRef
25.
Volinsky CT, Raftery AE: Bayesian information criterion for censored survival models. Biometrics. 2000, 56 (1): 256-262. 10.1111/j.0006-341X.2000.00256.x.CrossRefPubMed
26.
Burnham K, Anderson DR: Model Selection and Multimodel inference: a practical information-theoretic approach. 2002, New York , Springer, 2
27.
R, Developement, Core, Team: R: A language and environment for statistical computing. 2004, Vienna , R Foundation for Statistical Computing
28.
Piyathilake CJ, Frost AR, Weiss H, Manne U, Heimburger DC, Grizzle WE: The expression of Ep-CAM (17-1A) in squamous cell cancers of the lung. Hum Pathol. 2000, 31 (4): 482-487. 10.1053/hp.2000.6711.CrossRefPubMed
29.
Hosch SB, Scheunemann P, Izbicki JR: Minimal residual disease in non-small-cell lung cancer. Semin Surg Oncol. 2001, 20 (4): 278-281. 10.1002/ssu.1045.CrossRefPubMed
30.
Passlick B, Izbicki JR, Kubuschok B, Nathrath W, Thetter O, Pichlmeier U, Schweiberer L, Riethmuller G, Pantel K: Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer. J Clin Oncol. 1994, 12 (9): 1827-1832.PubMed
31.
Klein CA, Blankenstein TJ, Schmidt-Kittler O, Petronio M, Polzer B, Stoecklein NH, Riethmuller G: Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet. 2002, 360 (9334): 683-689. 10.1016/S0140-6736(02)09838-0.CrossRefPubMed
32.
Hosch S, Kraus J, Scheunemann P, Izbicki JR, Schneider C, Schumacher U, Witter K, Speicher MR, Pantel K: Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer. Cancer Res. 2000, 60 (24): 6836-6840.PubMed
33.
Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O: The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004, 23 (34): 5748-5758. 10.1038/sj.onc.1207610.CrossRefPubMed
34.
Songun I, Litvinov SV, van de Velde CJ, Pals ST, Hermans J, van Krieken JH: Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer. Br J Cancer. 2005, 92 (9): 1767-1772. 10.1038/sj.bjc.6602519.CrossRefPubMedPubMedCentral
35.
Seligson DB, Pantuck AJ, Liu X, Huang Y, Horvath S, Bui MH, Han KR, Correa AJ, Eeva M, Tze S, Belldegrun AS, Figlin RA: Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma. Clin Cancer Res. 2004, 10 (8): 2659-2669. 10.1158/1078-0432.CCR-1132-03.CrossRefPubMed
36.
Basak S, Speicher D, Eck S, Wunner W, Maul G, Simmons MS, Herlyn D: Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine homologue. J Natl Cancer Inst. 1998, 90 (9): 691-697. 10.1093/jnci/90.9.691.CrossRefPubMed
37.
Riethmuller G, Schneider-Gadicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, et al: Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet. 1994, 343 (8907): 1177-1183. 10.1016/S0140-6736(94)92398-1.CrossRefPubMed
38.
Naundorf S, Preithner S, Mayer P, Lippold S, Wolf A, Hanakam F, Fichtner I, Kufer P, Raum T, Riethmuller G, Baeuerle PA, Dreier T: In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment. Int J Cancer. 2002, 100 (1): 101-110. 10.1002/ijc.10443.CrossRefPubMed
39.
Hartung G, Hofheinz RD, Dencausse Y, Sturm J, Kopp-Schneider A, Dietrich G, Fackler-Schwalbe I, Bornbusch D, Gonnermann M, Wojatschek C, Lindemann W, Eschenburg H, Jost K, Edler L, Hochhaus A, Queisser W: Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study. Onkologie. 2005, 28 (6-7): 347-350. 10.1159/000084595.PubMed
40.
Punt CJ, Nagy A, Douillard JY, Figer A, Skovsgaard T, Monson J, Barone C, Fountzilas G, Riess H, Moylan E, Jones D, Dethling J, Colman J, Coward L, MacGregor S: Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Lancet. 2002, 360 (9334): 671-677. 10.1016/S0140-6736(02)09836-7.CrossRefPubMed
41.
Schlereth B, Fichtner I, Lorenczewski G, Kleindienst P, Brischwein K, da Silva A, Kufer P, Lutterbuese R, Junghahn I, Kasimir-Bauer S, Wimberger P, Kimmig R, Baeuerle PA: Eradication of tumors from a human colon cancer cell line and from ovarian cancer metastases in immunodeficient mice by a single-chain Ep-CAM-/CD3-bispecific antibody construct. Cancer Res. 2005, 65 (7): 2882-2889. 10.1158/0008-5472.CAN-04-2637.CrossRefPubMed
42.
Pantel K, Riethmuller G: Micrometastasis detection and treatment with monoclonal antibodies. Curr Top Microbiol Immunol. 1996, 213 ( Pt 3): 1-18.
Metadata
Title
Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker
Authors
Nikolas H Stoecklein
Annika Siegmund
Peter Scheunemann
Andreas M Luebke
Andreas Erbersdobler
Pablo E Verde
Claus F Eisenberger
Matthias Peiper
Alexander Rehders
Jan Schulte am Esch
Wolfram Trudo Knoefel
Stefan B Hosch
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-165

Other articles of this Issue 1/2006

BMC Cancer 1/2006 Go to the issue

Research article

Heat shock protein expression in canine malignant mammary tumours

Research article

Combined immunohistochemistry of β-catenin, cytokeratin 7, and cytokeratin 20 is useful in discriminating primary lung adenocarcinomas from metastatic colorectal cancer

Research article

Association of MTHFR gene polymorphisms with breast cancer survival

Case report

Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

Research article

High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study

Research article

Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits