title: Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201).
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.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
authors.forename: Karim
authors.initials: K
authors.lastname: El-Sahwi
authors.forename: Stefania
authors.initials: S
authors.lastname: Bellone
authors.forename: Emiliano
authors.initials: E
authors.lastname: Cocco
authors.forename: Francesca
authors.initials: F
authors.lastname: Casagrande
authors.forename: Marta
authors.initials: M
authors.lastname: Bellone
authors.forename: Maysa
authors.initials: M
authors.lastname: Abu-Khalaf
authors.forename: Natalia
authors.initials: N
authors.lastname: Buza
authors.forename: Fattaneh A
authors.initials: FA
authors.lastname: Tavassoli
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: Dominik
authors.initials: D
authors.lastname: Rüttinger
authors.forename: Dan-Arin
authors.initials: DA
authors.lastname: Silasi
authors.forename: Masoud
authors.initials: M
authors.lastname: Azodi
authors.forename: Peter E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D007074:Immunoglobulin G; D007376:Interleukin-2; D012333:RNA, Messenger; C460839:adecatumumab