Histological and Molecular Characterization of Mucin-Rich Gastrointestinal andMammary Carcinomas with a Focus on MUC1, MUC2, MUC4 and MUC5AC

Although mucin-producing carcinomas of the gastrointestinal tract and breast have
similar histological characteristics, their clinical behavior and prognosis vary. The
relationship of mucin gene product expression in the development of these clinical
differences is poorly understood. This study examines the histopathological
characteristics of gastrointestinal and breast mucin-producing carcinomas for the
expression of MUC1, MUC2, MUC4, and MUC5AC and their relationship to
patient outcome. A retrospective comparative study of 120 mucinous carcinomas
of the gastrointestinal tract and breast (60 in each group) was conducted. The
histopathological characteristics of the tumors were examined. MUC gene
expression was quantified by RT-qPCR in a subset of 60 cases. Overall survival
was evaluated in the RT-qPCR subset using Kaplan–Meier analysis and
multivariate Cox proportional hazards models. Gastrointestinal tumors exhibited
significantly higher histologic grade and greater necrosis compared with mammary
tumors (P < 0.01). MUC2 and MUC5AC were markedly overexpressed in
gastrointestinal carcinomas (P < 0.001 for both), whereas MUC1 and MUC4 were
expressed across both tumor types. In multivariate analysis, high expression of
MUC1 (hazard ratio = 2.18; 95% confidence interval [CI], 1.31–3.61; P = 0.003)
and MUC4 (HR = 1.89; 95% CI, 1.10–3.23; P = 0.017) was independently
associated with reduced overall survival. In contrast, MUC2 and MUC5AC
expression distinguished tumor origin but showed no prognostic significance (P >
0.05). Mucin gene expression profiles differ substantially between GI and
mammary mucin-rich carcinomas. MUC1 and MUC4 have prognostic relevance,
while MUC2 and MUC5AC aid in determining tumor origin. Integrating
histopathological evaluation with molecular profiling may improve diagnostic
accuracy and risk stratification in mucin-rich carcinomas.