Aberrant expression of muc1 mucin in ductal hyperplasia and ductal carcinoma In situ of the breast

Abstract

MUC1 mucin is a high molecular weight transmembrane glycoprotein expressed on the apical cell surface of normal glandular epithelia. In many human adenocarcinomas, this protein is up‐regulated and/or underglycosylated, and its expression changes from apical to the entire cell membrane. It is thought that entire cell membrane expression of MUC1 reduces cell–cell and cell–extracellular matrix interactions and therefore may facilitate invasive growth and development of metastases. In this study, we determined immunohistochemically the expression of normal and underglycosylated MUC1 in normal breast tissue (n = 8) and in a spectrum of breast lesions, including usual ductal hyperplasia (n = 23), atypical ductal hyperplasia (n = 7), and ductal carcinoma in situ (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, whereas SM3 and VU‐4‐H5 stain only underglycosylated forms. All cases showed apical positivity for 115D8 and 139H2. Entire cell membrane expression of fully (normal) glycosylated MUC1 was mainly found in DCIS lesions. Apical staining of SM3 was found in 38% of normal cases and 60% of the ductal lesions 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 hyperplasia (3%). Membrane expression of underglycosylated MUC1 was found only 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 breast. This finding implies that these lesions with aberrant expression are at higher risk for developing subsequent invasive breast carcinoma. Int. J. Cancer (Pred. Oncol.) 84:466–469, 1999. © 1999 Wiley‐Liss, Inc.

Antibody-Guided In Vivo Imaging for Early Detection of Mammary Gland Tumors

“…In tumor cells including breast tumors, these motifs are hypoglycosylated and the MUC1 distribution is altered [11], [12], [13]. In addition, as early as hyperplasia stages, the distribution and glycosylation of MUC1 are altered and the cell-cell organization disrupted [12], [14]. As such, MUC1 is viewed as a key therapeutic target in patients with breast cancer [15], [16].…”

Labeling of Anti-MUC-1 Binding Single Chain Fv Fragments to Surface Modified Upconversion Nanoparticles for an Initial in Vivo Molecular Imaging Proof of Principle Approach

“…However, the developed approach is of use because patients who are at high risk to develop, e.g., breast cancer [33] express the MUC-1 antigen at an early stage. Thus, early cancer detection, staging and treatment-follow up via imaging is highly beneficial and had been shown previously with a dual labeled MRI/fluorescence probe [34].…”

Current modalities in cancer immunotherapy: Immunomodulatory antibodies, CARs and vaccines

“…Yonezawa, Higashi, Yamada, & Goto, 2008). Abnormally glycosylated MUC1 has also been found on breast ductal carcinomas in situ , as well as adenoma of the colon, a precursor to colon cancer (Ajioka, Watanabe, & Jass, 1997; Mommers et al, 1999). Recent studies to find new antigens expressed on cancer stem cells and premalignant lesions looking at colon adenoma and colorectal cancer microarrays identified 160 up-regulated genes compared to normal colon (Broussard et al, 2013).…”