CHANGED EXPRESSION OF 9-O-ACETYL GD3 (CDW60) IN BENIGN AND ATYPICAL PROLIFERATIVE LESIONS AND CARCINOMAS OF THE HUMAN BREAST

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.