Expression of Underglycosylated MUC1 Antigen in Cancerous and Adjacent Normal Breast Tissues

Underglycosylated mucin 1 antigen (uMUC1) is aberrantly expressed in breast cancer. Using tissue microarray (TMA) and fresh-frozen breast cancer tissues, we analyzed its expression and found changes associated with higher tumor grade. We also observed changes in tissues adjacent to tumor but identified as normal on pathology reports. These findings suggest that uMUC1 can indeed serve as an early diagnostic marker. Introduction: Mucin 1 antigen (MUC1) is a high-molecular-weight transmembrane glycoprotein with an aberrant expression profile in various malignancies, including breast cancer. Its increased overexpression and underglycosylation in breast cancer is associated with tumor invasiveness and metastatic potential. In this study, we took the next step toward establishing MUC1 as a potential diagnostic, prognostic, and therapeutic target by investigating its expression and posttranslational modification (glycosylation/sialylation). Patients and Methods: In these studies we used a breast cancer tissue microarray (TMA) and fresh-frozen multistage breast cancer tissues. We analyzed in detail the expression of normal and underglycosylated/sialated MUC1 by immunohistochemical techniques, real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and various analytic techniques. Results: We found that changes in cellular localization as well as in upregulation and/or underglycosylation of MUC1 were associated with higher tumor grade. A key finding in this study was that underglycosylated MUC1 (uMUC1) overexpression and sialation were observed in tissues adjacent to tumor but identified as normal on pathology reports. Conclusions: These findings suggest that uMUC1 can indeed be used as an early diagnostic marker and provide additional insights into breast cancer management. Clinical Breast Cancer, Vol. 13, No. 2, 109-18 (C) 2013 Elsevier Inc. All rights reserved.