Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201)
Document Type
Article
Publication Title
Molecular cancer therapeutics
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.
First Page
57
Last Page
66
DOI
10.1158/1535-7163.MCT-09-0675
Publication Date
1-1-2010
Recommended Citation
El-Sahwi, Karim; Bellone, Stefania; Cocco, Emiliano; Casagrande, Francesca; Bellone, Marta; Abu-Khalaf, Maysa; Buza, Natalia; Tavassoli, Fattaneh A.; Hui, Pei; Rüttinger, Dominik; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Rutherford, Thomas J.; Pecorelli, Sergio; and Santin, Alessandro D., "Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201)" (2010). Obstetrics and Gynecology. 154.
https://scholar.bridgeporthospital.org/obgyn/154
Identifier
20053761 (pubmed); NIHMS159166 (mid); PMC2806489 (pmc); 10.1158/1535-7163.MCT-09-0675 (doi); 1535-7163.MCT-09-0675 (pii)