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Journal of Histochemistry and Cytochemistry, Vol. 45, 1547-1558, Copyright © 1997 by The Histochemical Society, Inc.

ARTICLE

Mucins (MUC1 and MUC3) of Gastrointestinal and Breast Epithelia Reveal Different and Heterogeneous Tumor-associated Aberrations in Glycosylation

Yi Caoa, Dietmar Blohmb, B. Michael Ghadimic, Peter Stosiekd, Pei-Xiang Xinge, and Uwe Karstena
a Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
b Biotechnology and Molecular Genetics, University of Bremen, Bremen, Germany
c Robert Rössle Clinic, Rudolf Virchow Klinikum, Humboldt University, Berlin, Germany
d Institute of Pathology, Carl Thiem Klinikum, Cottbus, Germany
e Austin Research Institute, Heidelberg, Australia

Correspondence to: Uwe Karsten, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str.10, D 13122 Berlin-Buch, Germany.

In a comprehensive study, we examined the expression of the membrane and secretory mucins MUC1 and MUC3, respectively, in normal and neoplastic gastrointestinal and breast epithelia before and after specific alterations of their glycan structures by neuraminidase, {alpha}-fucosidase, or carbohydrate-specific periodate oxidation. MUC1 mRNA was also identified in normal colorectal tissues by in situ hybridization. The data revealed that normal colorectal epithelia express both MUC1 mRNA and protein, which were detectable after periodate oxidation with all tested MUC1-specific antibodies. During tumorigenesis in the colon, MUC1 became recognizable without periodate treatment concomitantly with highly dysplastic lesions and the malignant state. In the breast, in which MUC1 is detectable with most antibodies in normal epithelium as well as in carcinomas, staining could be enhanced by pretreatment with periodate and casually by enzyme treatments. MUC3 was detectable in normal and neoplastic colorectal tissues and was more intensely stained after periodate oxidation. It was absent in normal breast even after pretreatment but was expressed in seven of 20 breast carcinomas. Therefore, incomplete glycosylation, abnormal distribution, and ectopic expression of mucins are characteristics of malignancy. Periodate oxidation may be widely applicable to immunohistochemistry for examining changes in glycosylation and for detecting antigens masked by glycans. (J Histochem Cytochem 45:1547-1557, 1997)

Key Words: MUC1, MUC3, immunohistochemistry, in situ hybridization, carbohydrate, periodate oxidation, gastrointestinal tract, breast, tumor


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