Prognostic and Clinicopathological Significance of Mucin 1 and Mucin 4 Expression in Oral Squamous Cell Carcinoma: A Systematic Review

Mucin 1 (MUC1) and mucin 4 (MUC4) are transmembrane mucins implicated in epithelial differentiation, cell signaling, tumor progression, and metastatic behavior.Their expression in oral squamous cell carcinoma (OSCC) has been investigated as a potential indicator of clinicopathological characteristics and prognosis.However, the reported findings remain inconsistent.This systematic review evaluated the clinicopathological and prognostic significance of MUC1 and MUC4 expression in OSCC patients.A comprehensive literature search was performed in PubMed/MEDLINE, Scopus, Web of Science Core Collection, Embase, and Google Scholar from database inception to May 31, 2026.Human studies evaluating MUC1 and/or MUC4 expression in histopathologically confirmed OSCC were eligible.Data regarding study characteristics, immunohistochemical methods, expression patterns, clinicopathological associations, coexpression, and prognostic outcomes were extracted and synthesized.Two reviewers independently assessed the methodological quality of the included observational studies using the Newcastle-Ottawa Scale, which evaluates selection, comparability, and outcome/exposure ascertainment.Thirteen studies, involving different populations and methodological approaches, were included.MUC1 expression is generally higher in OSCC than in the normal oral mucosa and is associated in several studies with nodal involvement, advanced stage, vascular invasion, and tumor progression.MUC4 expression was similarly associated with tumor stage, nodal status, and invasive characteristics in larger cohorts, although smaller studies have frequently reported greater expression in well-differentiated tumors.Concurrent MUC1/MUC4 expression has been observed in several studies and is associated with adverse clinicopathological features and poor survival in the largest prognostic cohort.However, substantial heterogeneity in antibody clones, staining thresholds, scoring systems, study populations, and outcome definitions, together with overlap among prognostic cohorts and limited direct comparisons, and the absence of quantitative synthesis, limits the interpretation of the findings.Overall, MUC1 and MUC4 show potential as adjunctive biomarkers in OSCC; however, their independent prognostic value and clinical utility require validation in standardized, adequately powered, multicenter studies.