Apc Alterations in Papillary Thyroid Carcinoma: Molecular Mechanisms, Clinical Implications, and Future Perspective Publisher



Soltani A ; Razi F ; Abdollahi A
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer which is characterized by a complex of molecular panels involving genetic and signaling pathway alterations. The major molecular driver of PTC is MAPK signaling pathway, including BRAF, RAS, and RET/PTC, but new evidence suggests the role of Wnt/β-catenin signaling pathway dysregulation in thyroid tumor development and tumor progression. The adenomatous polyposis coli (APC) gene as an important tumor suppressor gene that negatively regulates β-catenin, has attracted attention due to its role in familial adenomatous polyposis (FAP)-associated thyroid carcinoma. This review summarizes the structure and biological function of APC gene, its role in Wnt/β-catenin signaling pathway, and its contribution to the molecular pathogenesis of PTC. Furthermore, the contribution of germline and somatic APC alterations to FAP-associated thyroid tumors, and the molecular mechanisms linking APC dysregulation to thyroid carcinogenesis are discussed. In addition, we reviewed the potential diagnostic, prognostic, and therapeutic implications of APC-related molecular alterations, including their relevance to molecular testing, precision medicine, genetic counseling, and surveillance strategies. Despite the uncommon prevalence of APC mutations in sporadic PTC, some studies suggest the role of APC-related molecular abnormalities in tumor progression and the emergence of aggressive clinicopathological disease subtypes. In addition, APC mutations may have significant clinical value when integrated with other molecular markers of thyroid carcinogenesis. However, the definite clinical significance of APC mutations in PTC emergence is not fully understood, and additional prospective and translational studies are required to elucidate their biological and clinical advantages in diagnosis, prognosis, targeted therapy, and individualized patient management. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.