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Overexpression of Epithelial Cell Adhesion Molecule in Primary, Metastatic, and Recurrent/Chemotherapy-Resistant Epithelial Ovarian Cancer: Implications for Epithelial Cell Adhesion Molecule-Specific Immunotherapy
  1. Stefania Bellone, PhD*,
  2. Eric R. Siegel, MS,
  3. Emiliano Cocco, MS*,
  4. Marilisa Cargnelutti, MS*,
  5. Dan-Arin Silasi, MD*,
  6. Masoud Azodi, MD*,
  7. Peter E. Schwartz, MD*,
  8. Thomas J. Rutherford, MD*,
  9. Sergio Pecorelli, MD and
  10. Alessandro D. Santin, MD*
  1. *Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT;
  2. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR; and
  3. Division of Gynecologic Oncology, University of Brescia, Brescia, Italy.
  1. Address correspondence and reprint requests to Alessandro D. Santin, MD, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, Room 305 LSOG, 333 Cedar St, PO Box 208063, New Haven, CT 06520-8063. E-mail: alessandro.santin{at}yale.edu.

Abstract

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.

  • Epithelial cell adhesion molecule
  • Ovarian tumor marker
  • Epithelial ovarian cancer
  • Quantitative reverse transcription-polymerase chain reaction
  • Immunohistochemistry

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Footnotes

  • Supported by grants from the Nocivelli, the Camillo Golgi, and the Berlucchi Foundations Brescia, Italy, and grants from the Italian Institute of Health (ISS), Rome, Italy.

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