Enhanced expression of sulfatide, a sulfated glycolipid, in well-differentiated endometrial adenocarcinoma.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Departments of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Taro
T
Sugiyama
Masaki
M
Miyazawa
Mikio
M
Mikami
Yumiko
Y
Goto
Yoshihiro
Y
Nishijima
Masae
M
Ikeda
Takeshi
T
Hirasawa
Toshinari
T
Muramatsu
Susumu
S
Takekoshi
Masao
M
Iwamori
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D002855:Chromatography, Thin Layer; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D013433:Sulfoglycosphingolipids; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase