This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Drapkin, R. Articles by Hecht, J. L. Search for Related Content PubMed PubMed Citation Articles by Drapkin, R. Articles by Hecht, J. L.

Human Epididymis Protein 4 (HE4) Is a Secreted Glycoprotein that Is Overexpressed by Serous and Endometrioid Ovarian Carcinomas

¹ Department of Cancer Biology, Dana-Farber Cancer Institute; ² Department of Pathology, Division of Women's and Perinatal Pathology and ³ Laboratory of Gynecologic Oncology, Division of Gynecologic Oncology, Brigham and Women's Hospital; ⁴ Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and ⁵ Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas

Requests for reprints: Ronny Drapkin, Department of Cancer Biology, SM810 Dana-Farber Cancer Institute, One Jimmy Fund Way, Boston, MA 02115. Phone: 617-632-4380; Fax: 617-632-4381; Email: ronny_drapkin{at}dfci.harvard.edu.

Among the genes most commonly identified in gene expression profiles of epithelial ovarian carcinomas (EOC) is the gene for human epididymis protein 4 (HE4). To ascertain its clinical utility, we did a comprehensive assessment of HE4 protein expression in benign and malignant ovarian and nonovarian tissues by immunohistochemistry. In comparison with normal surface epithelium, which does not express HE4, we found that cortical inclusion cysts lined by metaplastic Mullerian epithelium abundantly express the protein. Its expression in tumors was restricted to certain histologic subtype: 93% of serous and 100% of endometrioid EOCs expressed HE4, whereas only 50% and 0% of clear cell carcinomas and mucinous tumors, respectively, were positive. Tissue microarrays revealed that the majority of nonovarian carcinomas do not express HE4, consistent with our observation that HE4 protein expression is highly restricted in normal tissue to the reproductive tracts and respiratory epithelium. HE4 is predicted to encode a secreted protein. Using reverse transcription-PCR, we identified ovarian cancer cell lines that endogenously overexpress HE4. Cultured medium from these cells revealed a secreted form of HE4 that is N-glycosylated. This observation is consistent with the recent report that HE4 circulates in the bloodstream of patients with EOC. Therefore, HE4 is a secreted glycoprotein that is overexpressed by serous and endometrioid EOCs. Its expression in cortical inclusion cysts suggests that formation of Mullerian epithelium is a prerequisite step in the development of some types of EOCs.

Key Words: ovarian cancer • epididymis • WAP • glycosylation • HE4

This article has been cited by other articles:

				K. A. Lowe, C. Shah, E. Wallace, G. Anderson, P. Paley, M. McIntosh, M. R. Andersen, N. Scholler, L. Bergan, J. Thorpe, et al. Effects of Personal Characteristics on Serum CA125, Mesothelin, and HE4 Levels in Healthy Postmenopausal Women at High-Risk for Ovarian Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2008; 17(9): 2480 - 2487. [Abstract] [Full Text] [PDF]

				N. Scholler, K. A. Lowe, L. A. Bergan, A. V. Kampani, V. Ng, R. M. Forrest, J. D. Thorpe, J. A. Gross, B. M. Garvik, R. Drapkin, et al. Use of Yeast-Secreted In vivo Biotinylated Recombinant Antibodies (Biobodies) in Bead-Based ELISA Clin. Cancer Res., May 1, 2008; 14(9): 2647 - 2655. [Abstract] [Full Text] [PDF]

				F. A. Simpkins, N. M. Devoogdt, N. Rasool, N. E. Tchabo, E. U. Alejandro, M. M.R.N. Kamrava, and E. C. Kohn The alarm anti-protease, secretory leukocyte protease inhibitor, is a proliferation and survival factor for ovarian cancer cells Carcinogenesis, March 1, 2008; 29(3): 466 - 472. [Abstract] [Full Text] [PDF]

				A. B. Tchagang, A. H. Tewfik, M. S. DeRycke, K. M. Skubitz, and A. P.N. Skubitz Early detection of ovarian cancer using group biomarkers Mol. Cancer Ther., January 1, 2008; 7(1): 27 - 37. [Abstract] [Full Text] [PDF]

				C. P. Crum, R. Drapkin, D. Kindelberger, F. Medeiros, A. Miron, and Y. Lee Lessons from BRCA: The Tubal Fimbria Emerges as an Origin for Pelvic Serous Cancer Clin. Med. Res., March 1, 2007; 5(1): 35 - 44. [Abstract] [Full Text] [PDF]

				N. Scholler, M. Crawford, A. Sato, C. W. Drescher, K. C. O'Briant, N. Kiviat, G. L. Anderson, and N. Urban Bead-based ELISA for validation of ovarian cancer early detection markers. Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2117 - 2124. [Abstract] [Full Text] [PDF]

				I. Simon, S. Zhuo, L. Corral, E. P. Diamandis, M. J. Sarno, R. L. Wolfert, and N. W. Kim B7-H4 Is a Novel Membrane-Bound Protein and a Candidate Serum and Tissue Biomarker for Ovarian Cancer Cancer Res., February 1, 2006; 66(3): 1570 - 1575. [Abstract] [Full Text] [PDF]