title: Trop-2 overexpression in poorly differentiated endometrial endometrioid carcinoma: implications for immunotherapy with hRS7, a humanized anti-trop-2 monoclonal antibody.
abstract: OBJECTIVE
  We evaluated the expression of human trophoblast cell surface marker (Trop-2) in endometrial endometrioid carcinoma (EEC) and the potential application of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a therapeutic agent against poorly differentiated EEC.
  
  
  METHODS
  Trop-2 expression was evaluated by immunohistochemistry in 131 EEC with different degrees of differentiation and 32 normal endometrial controls (NEC). Trop-2 expression was also evaluated by quantitative real-time polymerase chain reaction and flow cytometry in 3 primary EEC cell lines derived from patients harboring poorly differentiated EEC. Finally, the sensitivity of grade 3 EEC cell lines to hRS7 antibody-dependent cellular cytotoxicity was tested in standard 5-hour Cr release assays.
  
  
  RESULTS
  Trop-2 expression was detected in 126 (96.2%) of 131 EEC samples. Tumor tissues showed markedly increased Trop-2 positivity compared with NEC (P = 0.001). Trop-2 expression was significantly higher in all grades of EEC versus NEC. Grade 3 tumors displayed significantly stronger Trop-2 immunostaining compared with grade 1 EEC (P = 0.01). High Trop-2 expression by quantitative real-time polymerase chain reaction and flow cytometry was found in 1 grade 3 EEC primary cell line (EEC-ARK-1). Unlike Trop-2-negative EEC cell lines, EEC-ARK-1 was found highly sensitive to hRS7-mediated antibody-dependent cellular cytotoxicity in vitro (range of killing, 33.9%-50.6%; P = 0.004). Human serum did not significantly inhibit hRS7-mediated cytotoxicity against EEC-ARK-1 (P = 0.773).
  
  
  CONCLUSIONS
  Trop-2 is highly expressed in EEC, and its expression is significantly higher in poorly differentiated EEC when compared with well-differentiated EEC. Primary grade 3 EECs overexpressing Trop-2 are highly sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel therapeutic agent for the treatment of high-grade EEC refractory to standard treatment modalities.
authors: Angelo Nocivelli Institute of Molecular Medicine, Division of Gynecologic Oncology.
authors: Eliana
authors: E
authors: Bignotti
authors: Antonella
authors: A
authors: Ravaggi
authors: Chiara
authors: C
authors: Romani
authors: Marcella
authors: M
authors: Falchetti
authors: Silvia
authors: S
authors: Lonardi
authors: Fabio
authors: F
authors: Facchetti
authors: Sergio
authors: S
authors: Pecorelli
authors: Joyce
authors: J
authors: Varughese
authors: Emiliano
authors: E
authors: Cocco
authors: Stefania
authors: S
authors: Bellone
authors: Peter E
authors: PE
authors: Schwartz
authors: Thomas J
authors: TJ
authors: Rutherford
authors: Alessandro D
authors: AD
authors: Santin
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000276:immunology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D012333:RNA, Messenger; C499380:TACSTD2 protein, human; D003165:Complement System Proteins