Familial adenomatous polyposis-associated thyroid cancer - A clinical, pathological, and molecular genetics study

We report two familial adenomatous polyposis (FAP) kindreds with thyroid ca ncer, harboring two apparently novel germline APC mutations. The clinical p henotype in the first kindred was typical of classical adenomatous polyposi s, whereas the second kindred exhibited an attenuated adenomatous polyposis phenotype. There was a female predominance with a mean age of 34 Fears (ra nge, 23-49) at cancer diagnosis, Multiple sections of four thyroid tumors f rom three FAP patients were analyzed in detail. Histological examination of thyroid tumors showed a range of morphological features. Some tumors exhib ited typical papillary architecture and were associated with multifocal car cinoma; in others, there were unusual areas of cribriform morphology, and s pindle-cell components with whorled architecture. Immunoreactivity for thyr oglobulin and high molecular weight keratins was strong. Somatic APC mutati on analysis revealed an insertion of a novel long interspersed nuclear elem ent-1-like sequence in one tumor sample, suggesting disruption of APC, In t hree FAP patients, ret/PTC-1 and I rett/PTC-3 were expressed in thyroid can cers. No positivity was observed for ret/PTC-2. p53 immunohistochemistry wa s positive in only one section of a recurrent thyroid tumor sample. Our dat a suggest that genetic alterations in FAP-associated thyroid cancer involve loss of function of APC along with the gain of function of ret/PTC, while alterations of p53 do not appear to be an early event in thyroid tumorigene sis.