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.
Highlights
Cancer of the uterine corpus is the most prevalent gynecologic tumor in women, with an estimated 40,100 cases and 7,470 deaths in the United States in 2008 [1]
To minimize the risk of contamination of uterine serous papillary carcinoma (USPC) RNA with that of normal cells or tumor cells with different histology, we extracted RNA to be evaluated for epithelial cell adhesion molecule (EpCAM) expression by qRT-PCR from primary USPC with single type differentiation
A total of 35 specimens including 6 flash-frozen normal endometria tissues, 24 primary, 4 metastatic, and 1 recurrent USPC were evaluated for EpCAM expression by qRT-PCR assays
Summary
Cancer of the uterine corpus is the most prevalent gynecologic tumor in women, with an estimated 40,100 cases and 7,470 deaths in the United States in 2008 [1]. The majority of cancers of the uterus are early stage, low-grade endometrioid tumors (i.e., type I). These neoplasms are frequently diagnosed in younger women, are associated. Type II endometrial cancers are poorly differentiated tumors, often with serous papillary or clear cell histology. Type II tumors account for a minority of endometrial cancers, the majority of relapses and deaths occur in this group of patients [2, 3]
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