Diagnostic Potential of Tn-MUC1 in Breast Cancer: A Novel Immunohistochemical Marker Reflecting Tumor Progression

Mucin 1 (MUC1) is a highly O-glycosylated transmembrane glycoprotein. Tumor-associated MUC1, characterized by aberrant O-linked glycans, is overexpressed in cancer cells; however, conventional MUC1 antibodies show limited specificity for tumor-associated glycan structures. Recently, a novel epitope-defined antibody (MUC1-Tn antigen epitope-defined antibody [MUC1-Tn ED Ab]) that specifically recognizes the Tn-MUC1 antigen was developed. In this study, we evaluated the potential of MUC1-Tn ED Abs as diagnostic markers of breast cancer. Tissue microarray sections from 124 patients with invasive breast carcinoma (IBC) and 26 whole tissue sections, including multiple neoplastic lesions-flat epithelial atypia (n = 24), ductal carcinoma in situ (n = 26), and IBC (n = 16)-were analyzed. Immunohistochemical distributions of Tn-MUC1 and MUC1 were assessed using the MUC1-Tn ED Ab (clone SN102) and a conventional antibody (clone Ma552), respectively. In tissue microarray analysis, Tn-MUC1 exhibited minimal immunoreactivity in nonneoplastic areas and high specificity for IBC. In IBC tissues, immunoreactivity with Tn-MUC1 was predominantly cytoplasmic, unlike conventional MUC1 staining observed in both the cytoplasm and membrane. In multilesion analysis, cytoplasmic Tn-MUC1 expression was rarely detected in nonneoplastic areas but progressively increased across flat epithelial atypia, ductal carcinoma in situ, and IBC. Knockdown assays in breast cancer cell lines demonstrated that core 1 β1,3-galactosyltransferase 1 (C1GALT1), an enzyme involved in galactosylation of the Tn antigen, significantly influenced the cellular localization of Tn-MUC1. This study demonstrates that Tn-MUC1, as detected by the MUC1-Tn ED Ab, has high specificity for breast cancer and may act as a novel immunohistochemical marker reflecting tumor progression.