Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201).

Authors

• Karim El-Sahwi
• Stefania Bellone
• Emiliano Cocco
• Francesca Casagrande
• Marta Bellone
• Maysa Abu-Khalaf
• Natalia Buza
• Fattaneh A Tavassoli
• Pei Hui
• Dominik Rüttinger
• Dan-Arin Silasi
• Masoud Azodi
• Peter E Schwartz
• Thomas J Rutherford
• Sergio Pecorelli
• Alessandro D Santin

Publication/Presentation Date

1-1-2010

Abstract

We evaluated the expression of epithelial cell adhesion molecule (EpCAM) and the potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real-time PCR and immunohistochemistry in a total of 56 USPC fresh-frozen biopsies and paraffin-embedded tissues. EpCAM surface expression was also evaluated by flow cytometry and immunohistochemistry in six USPC cell lines. Sensitivity to MT201 antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity was tested against a panel of primary USPC cell lines expressing different levels of EpCAM in standard 5-h (51)Cr release assays. EpCAM transcript was significantly overexpressed in fresh-frozen USPC when compared with normal endometrial cells (NEC). Median (minimum-maximum) copy number was 943.8 (31.5-1568.3) in tumor samples versus 12.9 (1.0-37.0) in NEC (P < 0.001). By immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC samples with significantly higher expression compared with NECs (P < 0.001). High surface expression of EpCAM was found in 83% (five out of six) of the USPC cell lines tested by flow cytometry. EpCAM-positive cell lines were found highly sensitive to MT201-mediated antibody-dependent cellular cytotoxicity in vitro, whereas primary USPC cell lines were resistant to natural killer cell-dependent cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma at mRNA and protein levels, and primary USPC are highly sensitivity to MT201-mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in patients harboring advanced/recurrent or metastatic USPC refractory to standard treatment modalities.

Volume

9

Issue

1

First Page

57

Last Page

66

ISSN

1538-8514

Published In/Presented At

El-Sahwi, K., Bellone, S., Cocco, E., Casagrande, F., Bellone, M., Abu-Khalaf, M., Buza, N., Tavassoli, F. A., Hui, P., Rüttinger, D., Silasi, D. A., Azodi, M., Schwartz, P. E., Rutherford, T. J., Pecorelli, S., & Santin, A. D. (2010). Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201). Molecular cancer therapeutics, 9(1), 57–66. https://doi.org/10.1158/1535-7163.MCT-09-0675

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

20053761

Department(s)

Administration and Leadership

Document Type

Article