Skip to main content
Springer Nature Link
Log in

High expression of epithelial cellular adhesion molecule in peritoneal metastasis of gastric cancer

  • Original Research
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

Intraperitoneally administrated epithelial cellular adhesion molecule (EpCAM) monoclonal antibody is a therapeutic agent in patients with malignant effusion in several types of carcinoma. However, the role of EpCAM in peritoneal metastasis (PM) lesions and primary lesions of gastric cancer (GC) is still unclear. Therefore, in this study, we investigated EpCAM expression in GC patients with PM. We investigated the expression of EpCAM in 35PM lesions and 104 biopsy samples as primary lesions. Immunohistochemical staining was performed using the Ventana Benchmark XT (Roche Diagnostics) system. EpCAM expression was evaluated by calculating the total immunostaining score, which is the product of the proportion score and the intensity score. Overexpression was defined as a total score greater than 4. All PM specimens showed overexpression of EpCAM, and GC cells in both the surface layer and the deep layer of the PM showed a high expression of EpCAM. Meanwhile, in the biopsy sample, the expression of EpCAM ranged from none to strong. The EpCAM score results for PM specimens and biopsy samples were 11.0 ± 2.0 and 6.9 ± 3.9, respectively. The difference between the scores was statistically significant (P < 0.05). The intraperitoneally administrated EpCAM antibody might have a anti-cancer effect in PM lesions of GC. Additionally, it can be assumed that only GC cells which express a high level of EpCAM might metastasize to the peritoneum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Corley DA, Buffler PA (2001) Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the Cancer Incidence in Five Continents database. Int J Epidemiol 30(6):1415–1425

    Article  PubMed  CAS  Google Scholar 

  2. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9(3):215–221. doi:10.1016/S1470-2045(08)70035-4

    Article  PubMed  CAS  Google Scholar 

  3. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E, Brachet A, Caillot JL, Faure JL, Porcheron J, Peix JL, Francois Y, Vignal J, Gilly FN (2000) Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 88(2):358–363. doi:10.1002/(SICI)1097-0142(20000115)88:2<358::AID-CNCR16>3.0.CO;2-O

    Article  PubMed  CAS  Google Scholar 

  4. 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 (2005) Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study. Onkologie 28(6–7):347–350. doi:10.1159/000084595

    Article  PubMed  CAS  Google Scholar 

  5. Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, Kononen J, Simon R, Sauter G, Baeuerle PA (2006) Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer 94(1):128–135. doi:10.1038/sj.bjc.6602924

    Article  PubMed  CAS  Google Scholar 

  6. Varga M, Obrist P, Schneeberger S, Muhlmann G, Felgel-Farnholz C, Fong D, Zitt M, Brunhuber T, Schafer G, Gastl G, Spizzo G (2004) Overexpression of epithelial cell adhesion molecule antigen in gallbladder carcinoma is an independent marker for poor survival. Clin Cancer Res 10(9):3131–3136

    Article  PubMed  CAS  Google Scholar 

  7. Baeuerle PA, Gires O (2007) EpCAM (CD326) finding its role in cancer. Br J Cancer 96(3):417–423. doi:10.1038/sj.bjc.6603494

    Article  PubMed  CAS  Google Scholar 

  8. Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, Dudnichenko AS, Aleknaviciene B, Razbadauskas A, Gore M, Ganea-Motan E, Ciuleanu T, Wimberger P, Schmittel A, Schmalfeldt B, Burges A, Bokemeyer C, Lindhofer H, Lahr A, Parsons SL (2010) The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer 127(9):2209–2221. doi:10.1002/ijc.25423

    Article  PubMed  CAS  Google Scholar 

  9. Linke R, Klein A, Seimetz D (2010) Catumaxomab: clinical development and future directions. MAbs 2(2):129–136

    Article  PubMed  Google Scholar 

  10. Imano M, Peng YF, Itoh T, Nishikawa M, Satou T, Yasuda A, Inoue K, Kato H, Shinkai M, Tsubaki M, Yasuda T, Imamoto H, Nishida S, Furukawa H, Takeyama Y, Okuno K, Shiozaki H (2012) A preliminary study of single intraperitoneal administration of paclitaxel followed by sequential systemic chemotherapy with S-1 plus paclitaxel for advanced gastric cancer with peritoneal metastasis. Anticancer Res 32(9):4071–4075

    PubMed  CAS  Google Scholar 

  11. Spizzo G, Obrist P, Ensinger C, Theurl I, Dunser M, Ramoni A, Gunsilius E, Eibl G, Mikuz G, Gastl G (2002) Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast cancer. Int J Cancer 98(6):883–888. doi:10.1002/ijc.10270

    Article  PubMed  CAS  Google Scholar 

  12. Wenqi D, Li W, Shanshan C, Bei C, Yafei Z, Feihu B, Jie L, Daiming F (2009) EpCAM is overexpressed in gastric cancer and its downregulation suppresses proliferation of gastric cancer. J Cancer Res Clin Oncol 135(9):1277–1285. doi:10.1007/s00432-009-0569-5

    Article  PubMed  Google Scholar 

  13. Passebosc-Faure K, Li G, Lambert C, Cottier M, Gentil-Perret A, Fournel P, Perol M, Genin C (2005) Evaluation of a panel of molecular markers for the diagnosis of malignant serous effusions. Clin Cancer Res 11(19 Pt 1):6862–6867. doi:10.1158/1078-0432.CCR-05-0043

    Article  PubMed  CAS  Google Scholar 

  14. Diaz-Arias AA, Loy TS, Bickel JT, Chapman RK (1993) Utility of BER-EP4 in the diagnosis of adenocarcinoma in effusions: an immunocytochemical study of 232 cases. Diagn Cytopathol 9(5):516–521

    Article  PubMed  CAS  Google Scholar 

  15. De Angelis M, Buley ID, Heryet A, Gray W (1992) Immunocytochemical staining of serous effusions with the monoclonal antibody Ber-EP4. Cytopathology 3(2):111–117

    Article  PubMed  Google Scholar 

  16. Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O (2004) The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene 23(34):5748–5758. doi:10.1038/sj.onc.1207610

    Article  PubMed  Google Scholar 

  17. Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ, Gillanders WE (2004) EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res 64(16):5818–5824. doi:10.1158/0008-5472.CAN-04-0754

    Article  PubMed  CAS  Google Scholar 

  18. Winter MJ, Nagelkerken B, Mertens AE, Rees-Bakker HA, Briaire-de Bruijn IH, Litvinov SV (2003) Expression of Ep-CAM shifts the state of cadherin-mediated adhesions from strong to weak. Exp Cell Res 285(1):50–58

    Article  PubMed  CAS  Google Scholar 

  19. Du W, Ji H, Cao S, Wang L, Bai F, Liu J, Fan D (2010) EpCAM: a potential antimetastatic target for gastric cancer. Dig Dis Sci 55(8):2165–2171. doi:10.1007/s10620-009-1033-8

    Article  PubMed  CAS  Google Scholar 

  20. Imano M, Imamoto H, Itoh T, Satou T, Peng YF, Yasuda A, Kato H, Shiraishi O, Shinkai M, Yasuda T, Takeyama Y, Okuno K, Shiozaki H (2012) Safety of intraperitoneal administration of paclitaxel after gastrectomy with en-bloc D2 lymph node dissection. J Surg Oncol 105(1):43–47

    Article  PubMed  CAS  Google Scholar 

  21. Sugarbaker PH, Yonemura Y (2000) Clinical pathway for the management of resectable gastric cancer with peritoneal seeding: best palliation with a ray of hope for cure. Oncology 58(2):96–107

    Article  PubMed  CAS  Google Scholar 

  22. Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Canc 5:67. doi:10.1186/1476-4598-5-67

    Article  Google Scholar 

  23. Alkatout I, Kabelitz D, Kalthoff H, Tiwari S (2008) Prowling wolves in sheep's clothing: the search for tumor stem cells. Biol Chem 389(7):799–811. doi:10.1515/BC.2008.094

    Article  PubMed  CAS  Google Scholar 

  24. Han ME, Jeon TY, Hwang SH, Lee YS, Kim HJ, Shim HE, Yoon S, Baek SY, Kim BS, Kang CD, Oh SO (2011) Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research. Cell Mol Life Sci 68(21):3589–3605. doi:10.1007/s00018-011-0672-z

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors express their appreciation to Dr. Harumasa Ohyanagi, vice board director of the University of KinDAI Himeji for his expert comments on the manuscript. We also wish to thank Mr. Tadao Uesugi and Miss Fusako Kamada for technical assistance.

Conflict of interest

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohno-higashi Osaka-Sayama, Osaka, Japan, 589-8511

    Motohiro Imano, Atsushi Yasuda, Kohei Nishiki, Hiroaki Kato, Osamu Shiraishi, Ying-Feng Peng, Masayuki Shinkai, Takushi Yasuda, Haruhiko Imamoto, Yoshifumi Takeyama, Hiroshi Furkawa, Kiyokata Okuno & Hitoshi Shiozaki

  2. Cancer Center, Kinki University Hospital, 377-2 Ohno-higashi Osaka-Sayama, Osaka, Japan, 589-8511

    Motohiro Imano & Yoshifumi Takeyama

  3. Department of Pathology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi Osaka-Sayama, Osaka, Japan, 589-8511

    Tatsuki Itoh & Takao Satou

  4. Division of Pharmacotherapy, Kinki University Faculty of Pharmacy, 3-4-1 Kowakae Higashi-Osaka, Osaka, Japan, 577-5802

    Masahiro Tsubaki & Shozo Nishida

Authors
  1. Motohiro Imano
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Tatsuki Itoh
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Takao Satou
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Atsushi Yasuda
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Kohei Nishiki
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Hiroaki Kato
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Osamu Shiraishi
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Ying-Feng Peng
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Masayuki Shinkai
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Masahiro Tsubaki
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Takushi Yasuda
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Haruhiko Imamoto
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Shozo Nishida
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Yoshifumi Takeyama
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Hiroshi Furkawa
    View author publications

    You can also search for this author inPubMed Google Scholar

  16. Kiyokata Okuno
    View author publications

    You can also search for this author inPubMed Google Scholar

  17. Hitoshi Shiozaki
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Motohiro Imano.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Imano, M., Itoh, T., Satou, T. et al. High expression of epithelial cellular adhesion molecule in peritoneal metastasis of gastric cancer. Targ Oncol 8, 231–235 (2013). https://doi.org/10.1007/s11523-012-0239-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-012-0239-4

Keywords