A. Gocht et al., CHANGED EXPRESSION OF 9-O-ACETYL GD3 (CDW60) IN BENIGN AND ATYPICAL PROLIFERATIVE LESIONS AND CARCINOMAS OF THE HUMAN BREAST, HISTOCHEM C, 110(3), 1998, pp. 217-229
Expression of gangliosides is affected in various ways by malignant ce
ll transformation. In the present study, we investigated the expressio
n of CDw60, a constituent of O-acetylated disialogangliosides, in beni
gn and atypical proliferative breast diseases, and preinvasive and inv
asive carcinomas by immunohistochemistry and thin-layer chromatography
(TLC). In normal ducts, antibodies to CDw60 (mAb M-T21) reacted to me
mbranes of the Golgi apparatus in the juxtaluminal cell compartment. A
similar polarized distribution of Golgi cisterns in epithelial cells
was observed in several benign lesions, i.e., fibroadenomas, intraduct
al papillomas, and gynecomastia. In contrast, blunt duct adenosis and
duct hyperplasia exhibited an abnormal cytosolic and cell surface stai
ning, whereas atypical duct hyperplasia showed randomly dispersed immu
noreactive Golgi cisterns, indicating loss of epithelial polarity. In
mammary carcinomas and in two breast carcinoma cell lines (MCF-7 and E
FM-19) the neoplastic cells contained CDw60-immunolabelled Golgi compl
exes, which were distributed in a disorderly fashion throughout the cy
toplasm, thus reflecting a loss of epithelial polarity. Additionally,
only well differentiated ductal carcinomas in situ or invasive ductal
carcinomas disclosed a strong cell surface labelling, which was absent
in lower differentiated carcinomas of the same types. In all carcinom
as, the intensity of CDw60 immunostaining decreased with progressing l
oss of differentiation (grade of dedifferentiation), as demonstrated b
y staining intensity in paraffin sections and by evaluation of the rel
ative amounts of extracted 9-O-acetyl GD3 by TLC. Our results indicate
that abnormal CDw60 expression is already detectable in benign prolif
erative breast lesions with different risk rates to develop into malig
nant lesions. Downregulation of CDw60 expression in poorly differentia
ted invasive carcinomas may be the consequence of loss of cell functio
ns usually associated with poor prognosis.