A Descriptive Summary of Tumor-Associated MUC1 (TA-MUC1) Expression in Epithelial Malignancies: A Systematic Review...

Tumor-associated MUC1 (TA-MUC1) is a hypoglycosylated variant of MUC1 that is aberrantly expressed in many epithelial malignancies. Its limited presence in normal tissues and immunogenic properties suggest potential as a target for antibody-drug conjugates and cancer immunotherapy. However, the clinicopathological spectrum and therapeutic context of TA-MUC1-positive tumors remain insufficiently characterized. We conducted a systematic review of case reports and case series describing immunohistochemically confirmed TA-MUC1 expression in malignant tumors. A total of 73 individual cases from 61 publications were included. Data extraction covered demographics, tumor features, TA-MUC1 expression, treatments, outcomes, and associated biomarkers. TA-MUC1 expression was identified across a wide range of tumor types, most frequently in gastrointestinal, breast, and gynecologic cancers, but also in less common malignancies such as sarcomatoid carcinoma and pleural mesothelioma. Expression was frequently retained in metastatic sites. Immunohistochemical staining varied in intensity and methodology, with strong expression often associated with recurrence or aggressive clinical behavior. Multimodal therapy was commonly reported. Across cases, progression-free survival (PFS) was available in 56 of 73 (76.7%) cases. Among these, 47 of 56 (83.9%) had a documented progression event, whereas nine of 56 (16.1%) were censored (progression-free at last follow-up). The median PFS was 12.0 months (IQR 6.0-19.5; range 0.0-118.0 months). Overall survival (OS) was available in 56 of 73 (76.7%) cases. Among these, 14 of 56 (25.0%) deaths were reported, and 42 of 56 (75.0%) observations were censored (alive at last follow-up). The median OS was 12.0 months (IQR 8.0-26.0; range 0.5-118.0 months). Co-expression with biomarkers such as programmed death-ligand 1 (PD-L1) and human epidermal growth factor receptor 2 (HER2) was occasionally observed. These findings demonstrate that TA-MUC1 has been documented in diverse malignancies, including rare and metastatic presentations. The descriptive evidence supports its potential relevance as a therapeutic target and highlights the need for standardized evaluation and prospective studies.