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 antibodydependent 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 51Cr 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.
Overexpression of EpCAM in uterine serous papillary carcinoma : implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201) / K. El-Sahwi, S. Bellone, E. Cocco, F. Casagrande, M. Bellone, M. Abu-Khalaf, N. Buza, F.A. Tavassoli, P. Hui, D. Rüttinger, D.A. Silasi, M. Azodi, P.E. Schwartz, T.J. Rutherford, S. Pecorelli, A.D. Santin. - In: MOLECULAR CANCER THERAPEUTICS. - ISSN 1535-7163. - 9:1(2010 Jan), pp. 57-66.
|Titolo:||Overexpression of EpCAM in uterine serous papillary carcinoma : implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201)|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||gen-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1158/1535-7163.MCT-09-0675|
|Appare nelle tipologie:||01 - Articolo su periodico|