Expression of
gangliosides is affected in various ways by malignant cell transformation. In the present study, we investigated the expression of CDw60, a constituent of O-acetylated
disialogangliosides, in benign and atypical proliferative
breast diseases, and preinvasive and invasive
carcinomas by immunohistochemistry and thin-layer chromatography (TLC). In normal ducts,
antibodies to CDw60 (mAb M-T21) reacted to membranes 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,
intraductal papillomas, and
gynecomastia. In contrast, blunt duct adenosis and duct
hyperplasia exhibited an abnormal cytosolic and cell surface staining, whereas atypical duct
hyperplasia showed randomly dispersed immunoreactive Golgi cisterns, indicating loss of epithelial polarity. In mammary
carcinomas and in two
breast carcinoma cell lines (MCF-7 and EFM-19) the neoplastic cells contained CDw60-immunolabelled Golgi complexes, which were distributed in a disorderly fashion throughout the cytoplasm, 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
carcinomas, the intensity of CDw60 immunostaining decreased with progressing loss of differentiation (grade of dedifferentiation), as demonstrated by staining intensity in
paraffin sections and by evaluation of the relative amounts of extracted 9-O-acetyl GD3 by TLC. Our results indicate that abnormal CDw60 expression is already detectable in benign proliferative breast lesions with different risk rates to develop into malignant lesions. Downregulation of CDw60 expression in poorly differentiated invasive
carcinomas may be the consequence of loss of cell functions usually associated with poor prognosis.