Aberrant expression of MUC1 mucin in ductal hyperplasia and ductal carcinoma in situ of the breast

MUC1 mucin is a high molecular weight transmembrane glycoprotein expressed on the apical cell surface of normal glandular epithelia. In many human ade nocarcinomas, this protein is up-regulated and/or underglycosylated, and it s expression changes from apical to the entire cell membrane. It is thought that entire cell membrane expression of MUC1 reduces cell-cell and cell-ex tracellular matrix interactions and therefore may facilitate invasive growt h and development of metastases. In this study, we determined immunohistoch emically the expression of normal and underglycosylated MUC1 in normal brea st tissue (n = 8) and in a spectrum of breast lesions, including usual duct al hyperplasia (n = 23), atypical ductal hyperplasia (n = 7), and ductal ca rcinoma in site (DCIS) (n = 22). We used 4 monoclonal antibodies; 115D8 is directed to a glycopeptide, the other 3 to the peptide core of the molecule , of which 139H2 is not affected by the degree of glycosylation of MUC1, wh ereas SM3 and VU-4-H5 stain only underglycosylated forms. All cases showed apical positivity for 115D8 and 139H2. Entire cell membrane expression of f ully (normal) glycosylated MUC1 was mainly found in DCIS lesions. Apical st aining of SM3 was found in 38% of normal cases and 60% of the ductal lesion s with no difference between the different subgroups. Apical staining of VU -4-H5 was found more often in DCIS (27%) than in normal tissue or ductal hy perplasia (3%). Membrane expression of underglycosylated MUC1 was found onl y in poorly differentiated DCIS. In conclusion, aberrant expression of MUC1 , i.e., on the entire cell membrane and/or underglycosylated forms, can be found in ductal hyperplasia with atypia and especially in DCIS of the breas t. This finding implies that these lesions with aberrant expression are at higher risk for developing subsequent invasive breast carcinoma. Int. J. Ca ncer (Pred. Oncol.) 84:466-469, 1999. (C) 1999 Wiley-Liss, Inc.