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Different Levels of Sialyl-Tn Antigen Expressed on MUC16 in Patients With Endometriosis and Ovarian Cancer
  1. Kaoru Akita, PhD*,
  2. Shuhei Yoshida, MSc*,
  3. Yuzuru Ikehara, MD, PhD,
  4. Sayumi Shirakawa, MSc,
  5. Munetoyo Toda, PhD*,
  6. Mizue Inoue, PhD*,
  7. Jo Kitawaki, MD, PhD,
  8. Hayao Nakanishi, MD, PhD§,
  9. Hisashi Narimatsu, MD, PhD and
  10. Hiroshi Nakada, PhD*
  1. *Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto;
  2. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Open Space Laboratory Central 2, Tsukuba;
  3. Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto; and
  4. §Division of Oncological Pathology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan.
  1. Address correspondence and reprint requests to Hiroshi Nakada, PhD, Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan. E-mail: hnakada@cc.kyoto-su.ac.jp.

Abstract

Objective Although CA125 antigen is a useful marker for ovarian cancer, its expression is also elevated in endometriosis. The purpose of this study was to develop an assay method for evaluating differentially glycosylated MUC16 (CA125 core protein) in patients with endometriosis and ovarian cancer.

Materials and Methods We prepared MUC16-enriched fractions from peritoneal fluid of patients with endometriosis and conditioned medium of ovarian carcinoma-3 cells by gel filtration, and evaluated the expression of sialyl-Lea, Tn, and sialyl-Tn antigens by dot blot analysis. A sandwich enzyme-linked immunosorbent assay was developed to measure the level of sialyl-Tn antigen expressed on MUC16 (sTn/MUC16). The level of sTn/MUC16 was compared between patients with endometriosis (n = 21) and ovarian cancer (n = 36) and in ovarian cancers with different clinical diagnostic criteria. Furthermore, distribution of MUC16 and sialyl-Tn antigen in ovarian cancer tissues was observed immunohistochemically.

Results Sialyl-Tn antigen was markedly detectable in the MUC16-enriched fractions from conditioned medium of ovarian carcinoma-3 cells but negligible in those from the peritoneal fluid of the patients with endometriosis. The level of sTn/MUC16 determined by a sandwich enzyme-linked immunosorbent assay was significantly higher in the patients with ovarian cancer than that in the patients with endometriosis (P < 0.001). An elevated level of sTn/MUC16 was detected in 44% of the patients with ovarian cancer but not all the patients with endometriosis. This level increased more prominently in the patients with ovarian cancer than that of MUC16 as both the clinical stage and cytological grade advanced. An elevated level of sTn/MUC16 was frequently found in the patients with serous and endometrioid carcinomas. Consistent with this, sialyl-Tn antigen was colocalized with MUC16 in serous and endometrioid ovarian cancer tissues.

Conclusions Estimation of the sTn/MUC16 level may be useful for discriminating endometriosis from ovarian cancer and for evaluating the clinical stage, cytological grade, and histological type of ovarian cancer.

  • Ovarian cancer
  • Endometriosis
  • MUC16
  • Sialyl-Tn antigen
  • ELISA

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Footnotes

  • This study was supported by the Medical Glycomics (MG) project in New Energy and Industrial Technology Development Organization (NEDO) in Japan.

  • K. Akita, S. Yoshida, and Y. Ikehara contributed equally to this work.

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