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Familial papillary thyroid carcinoma (PTC) is a well recognized disease. However, genetic predisposition to familial PTC is rare and the molecular alterations at the origin of the pathology are unknown. The association between PTC and lymphocytic thyroiditis (LT) has been reported recently. We communicate here 6 cases of PTC associated with LT in 2 unrelated families. PTC was diagnosed on classical nuclear and architectural criteria. It was bilateral in 5 cases. Architecture was equally distributed between typical PTC and its follicular variant. LT was present in variable degrees, including in 4 cases, oncocytic metaplasia. Using the RT-PCR technique, we observed a RET/PTC rearrangement in the carcinomatous areas of patients of both families: PTC1 in family 1 and PTC3 in family 2 and a RET/PTC rearrangement in non-malignant thyroid tissue with LT in family 2. The RET/PTC band was weaker or absent in pure LT areas. Furthermore, using a polyclonal ret antibody, an apical or a diffuse cytoplasmic ret onc protein immunolabelling was observed in the three patients with RET/PTC1 rearrangement and in the three patients with RET/PTC3 rearrangement. In conclusion our data: (1) show the presence of a RET/PTC 1 or 3 rearrangement (depending on the family) together with a variable expression of ret protein in all the PTCs; (2) suggest that the molecular event at the origin of the PTCs seems to be particular to each one of the studied families; and (3) confirm that the ret proto-oncogene activating rearrangement(s) is an early event in the thyroid tumorigenic process and that it can be observed in association with LT.

Papillary thyroid carcinoma: 6 cases from 2 families with associated lymphocytic thyroiditis harbouring RET/PTC rearrangements