Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy

被引：80

作者：

Bellone, Stefania ^{[1
]}

Siegel, Eric R. ^{[2
]}

Cocco, Emiliano ^{[1
]}

Cargnelutti, Marilisa ^{[1
]}

Silasi, Dan-Arin ^{[1
]}

Azodi, Masoud ^{[1
]}

Schwartz, Peter E. ^{[1
]}

Rutherford, Thomas J. ^{[1
]}

Pecorelli, Sergio ^{[3
]}

Santin, Alessandro D. ^{[1
]}

机构：

[1] Yale Univ, Dept Obstet Gynecol & Reprod Sci, Sch Med, New Haven, CT 06520 USA

[2] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA

[3] Univ Brescia, Div Gynecol Oncol, Brescia, Italy

来源：

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER | 2009年 / 19卷 / 05期

关键词：

Epithelial cell adhesion molecule; Ovarian tumor market; Epithelial ovarian cancer; Quantitative reverse transcription-polymerase chain reaction; Immunohistochemistry; GENE-EXPRESSION PROFILES; EP-CAM; MONOCLONAL-ANTIBODY; IN-VITRO; IDENTIFICATION; CARCINOMAS; DIAGNOSIS; MARKER;

D O I：

10.1111/IGC.0b013e3181a8331f

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To evaluate the potential of epithelial cell adhesion molecule (Ep-CAM/TROP-1)-specific immunotherapy against epithelial ovarian carcinomas (EOCs), we have analyzed the expression of Ep-CAM at RNA and protein level in patients harboring primary, metastatic, and chemotherapy-resistant/recurrent EOC. Epithelial cell adhesion molecule expression was evaluated by real-time polymerase chain reaction and immunohistochemistry in 168 fresh-frozen biopsies and paraffin-embedded tissues. In addition, Ep-CAM Surface expression was evaluated by flow cytometry in several freshly established ovarian carcinoma cell lines derived from patients harboring tumors resistant to chemotherapy in vivo as well as in vitro. Epithelial cell adhesion molecule transcript was found significantly overexpressed in primary, metastatic, and recurrent EOC when compared with normal human ovarian surface epithelium cell lines and fresh-frozen normal ovarian tissue (P < 0.001). Similarly, by immunohistochemistry, Ep-CAM protein expression was found significantly higher in primary, metastatic, and recurrent EOC when compared with normal ovarian tissues. Of interest, metastatic/recurrent tumors were found to express significantly higher levels of Ep-CAM protein when compared with primary ovarian carcinomas (P < 0.001). Finally, a high surface expression of Ep-CAM was found in 100% (5/5) of the chemotherapy-resistant ovarian carcinoma cell lines studied by flow cytometry. These results demonstrate high Ep-CAM overexpression in ovarian carcinoma, especially in metastatic and recurrent/chemotherapy-resistant ovarian disease. The lack of Ep-CAM expression on the chelomic epithelium in the peritoneal cavity, combined with the recent development of fully human monoclonal antibodies against this Surface molecule, Suggest Ep-CAM as a promising target for antibody-mediated therapies in ovarian carcinoma patients harboring tumors refractory to standard treatment modalities.

引用

页码：860 / 866

页数：7

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