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Enhanced Expression of Sulfatide, a Sulfated Glycolipid, in Well-Differentiated Endometrial Adenocarcinoma
  1. Taro Sugiyama, MD*,
  2. Masaki Miyazawa, PhD*,
  3. Mikio Mikami, MD, PhD*,
  4. Yumiko Goto, MD*,
  5. Yoshihiro Nishijima, MD*,
  6. Masae Ikeda, MD*,
  7. Takeshi Hirasawa, MD, PhD*,
  8. Toshinari Muramatsu, MD, PhD*,
  9. Susumu Takekoshi, PhD and
  10. Masao Iwamori, PhD
  1. *Departments of Obstetrics and Gynecology and
  2. Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan; and
  3. Department of Biochemistry, Faculty of Science and Technology, Kinki University, Osaka, Japan.
  1. Address correspondence and reprint requests to Mikio Mikami, MD, PhD, Department of Obstetrics and Gynecology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1193, Japan. E-mail: mmikami{at}is.icc.u-tokai.ac.jp.

Abstract

Objectives It is well known that a poorly differentiated endometrial adenocarcinoma shows more rapid progression and a worse response to therapy than a well-differentiated endometrial adenocarcinoma. Qualitative and quantitative changes of cell surface glycolipids occur during neoplastic transformation. Sulfatide is one of the sulfated glycolipids in the cell membrane that may have an important role in various functions such as cell adhesion. To examine the molecular background of the morphological and biological features of well-differentiated and poorly differentiated cancer, we measured the levels of lipids, especially glycolipids, in tumor tissues from patients with endometrial carcinoma.

Materials and Methods We determined the composition of lipids and glycolipids in tumor tissues, investigated glycosyltransferase messenger RNA expression by the reverse transcription-polymerase chain reaction, and assessed the localization of galactosylceramide sulfotransferase (an enzyme involved in sulfatide biosynthesis) by immunohistochemical staining.

Results No significant differences were observed between well-differentiated and poorly differentiated cancer with respect to the levels of cholesterol ester, cholesterol, phospholipids, cholesterol sulfate, ceramides, neutral glycolipids of the globo series, and GM3 ganglioside. However, the amount of sulfatides in well-differentiated tumors was significantly greater than that in poorly differentiated tumors, which was confirmed by thin-layer chromatography and immunostaining with a monoclonal antisulfatide antibody. Altered expression of sulfatide was found to be secondary to a change of galactosylceramide sulfotransferase messenger RNA expression. Immunohistochemical staining revealed that galactosylceramide sulfotransferase expression was characteristically observed in glandular areas but not in solid areas.

Conclusion These findings suggest that sulfatide contributes to the well-differentiated phenotype of endometrial adenocarcinoma and that it is being expressed in normal uterine endometrium at sites of gland formation during the luteal phase, as we have previously reported.

  • Endometrioid adenocarcinoma
  • Glandular differentiation
  • Sulfatide
  • Carbohydrate sulfation
  • Tumor grade

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Footnotes

  • This work was supported in part by a grant-in-aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) (No. 23592465), MEXT- supported program for the Strategic Research Foundation at Private Universities, 2012–2014, and a grant from Tokai University Research Aid.

  • The authors declare no conflicts of interest.

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