Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma
International Journal of Gynecological Cancer, ISSN: 1048-891X, Vol: 21, Issue: 9, Page: 1613-1621
2011
- 31Citations
- 22Captures
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Metrics Details
- Citations31
- Citation Indexes31
- CrossRef31
- 30
- Captures22
- Readers22
- 22
Article Description
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. 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 51 Cr release assays. 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). 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.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1048891X24089291; http://dx.doi.org/10.1097/igc.0b013e318228f6da; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84857424342&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/21892093; https://linkinghub.elsevier.com/retrieve/pii/S1048891X24089291; http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00009577-201112000-00018; https://dx.doi.org/10.1097/igc.0b013e318228f6da; https://ijgc.bmj.com/content/21/9/1613; https://ijgc.bmj.com/lookup/doi/10.1097/IGC.0b013e318228f6da; https://ijgc.bmj.com/content/21/9/1613.abstract; https://ijgc.bmj.com/content/ijgc/21/9/1613.full.pdf; https://journals.lww.com/ijgc/Fulltext/2011/12000/Trop_2_Overexpression_in_Poorly_Differentiated.18.aspx; http://ijgc.bmj.com/lookup/doi/10.1097/IGC.0b013e318228f6da; http://content.wkhealth.com/linkback/openurl?an=00009577-201112000-00018
Elsevier BV
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