Genetics and Clinicopathological Findings in Thyroid Carcinomas Associated with Familial Adenomatous Polyposis

Abstract

The recent paper by Soravia et al 1 describes two kindreds with thyroid carcinoma associated with familial adenomatous polyposis (FAP). The former included three and the latter two FAP siblings with papillary thyroid carcinoma (PTC). The patients had a germline mutation of APC, the tumor suppressor gene responsible for FAP, 2 at codons 698 and 313, respectively, and activation of ret/PTC, a chimeric gene that is restricted to the papillary histotype, 3 in the thyroid tumoral tissue of three out of three subjects. Interestingly, ret/PTC was always found as its most frequent isoform, ret/PTC1. 3 This commentary discusses the issues of PTC as an extracolonic manifestation that is integral to FAP, genotype-phenotype correlations, the presence or absence of somatic mutations of the APC gene in the thyroid tumoral tissue, ret/PTC activation, possible cooperation among genes, histological significance of molecular alterations, and the natural history of these particular tumors.