Germline and somatic mutations of the APC gene in papillary thyroid carcinoma associated with familial adenomatous polyposis: Analysis of three cases and a review of the literature

Patients with familial adenomatous polyposis (FAP), which is caused by the dysfunction of the adenomatous polyposis coli (APC) protein, have the possibility of developing extracolonic manifestations, including thyroid cancer (TC), congenital hypertrophy of the retinal pigment epithelium, desmoid tumors, and gastric and duodenal adenomas. The pathogenesis of these disorders associated with FAP is considered to be affected by the site of the germline mutation on the APC gene as a genotype-phenotype correlation. Moreover, β-catenin binding sites consist of 20-amino acid repeats (20-AARs) in the APC protein, and they are essential for the development of colorectal adenomas and certain other extracolonic manifestations. The present study retrospectively analyzed the germline and somatic mutations of the APC gene in three papillary TC patients with FAP to analyze the association between the remaining number of 20-AARs and the development of TC. The mutation sites of two TCs did not include 20-AARs in each allele. In one patient, the remaining number of 20-AARs was two in the germline mutation and zero in the somatic mutation. Together with the data on 13 FAP-associated thyroid cancerous lesions in 3 FAP patients reported previously, the majority of the remaining numbers of 20-AARs was zero in the TC patients with FAP (13/16; 81.3%). Consequently, the APC/β-catenin signaling pathway may be strongly involved with the pathogenesis of TC with FAP. Further accumulation of FAP patients with TC will be required to confirm the molecular pathogenesis of TC.