Background: In cancers, key prognostic determinants such as clinical stage and mutational load are well recognized. However, mucinous adenocarcinomas (MACs) display distinct biological behavior, as a large proportion of their tumor volume consists of extracellular mucin, predominantly the MUC2 protein, rather than neoplastic cells. MUC2 provides a protective barrier for cancer cells against external factors, including chemotherapeutic agents and cytotoxic lymphocytes, while its anti-inflammatory and tumor-suppressive properties paradoxically support tumor persistence and immune evasion. Summary: Excessive mucin secretion and its viscoelastic properties facilitate rapid local expansion and dissemination into adjacent tissues. These effects are particularly significant in organs that open into body cavities, such as the colon and appendix, whereas they are less pronounced in confined organs such as the breast. In ductal organs, overexpression of MUC2 may promote early invasion through pressure-induced disruption of ductal structures. Key Messages: Consequently, in MACs, tumor location and organ architecture, alongside clinical stage and mutational profile, are critical determinants of biological behavior. Accurate differential diagnosis and therapeutic approaches should address both organ-specific pathways and MUC2-related mechanisms, including its structural, anti-inflammatory, and tumor-suppressive functions. MUC2-targeted therapies may thus represent a promising adjunct to conventional, organ-based treatment strategies.
Kemal Behzatoğlu (Tue,) studied this question.