LE CARATTERISTICHE MOLECOLARI DEL CARCINOMA PAPILLARE DELLA TIROIDE NON IODOFISSANTI

Background: Differentiated thyroid cancers (DTC) represent the most frequent endocrine cancer. They typically show an indolent behaviour and a good prognosis, mainly due to their capability to trap radioiodine (131-I), the most powerful therapeutic tool in these malignancies. Nevertheless, approximately one third of thyroid cancer metastases do not concentrate radioiodine. The most common genetic event in papillary thyroid carcinoma is a transversion in exon 15 of the BRAF gene which leads to a V600E aminoacid substitution (glutamic acid instead of valine) ranging from 36% to 48%. It has been demonstrated that cancers with the BRAF mutation have a more aggressive behaviour: the mutation is associated with more advanced initial tumor stage at diagnosis and with conversion into less differentiated or anaplastic cancers during the follow-up. BRAF could represent a new independent prognostic factor helpful to identify cancers that both tend to recur more frequently and lose the capability to trap radioiodine. The BRAF mutation is also associated with an increased expression of the glucose transporter (GLUT-1), suggesting the possibility to use 18-FDG-PET-CT examination during the follow-up. The objective of the study: 1) to estimate the frequency of the BRAF mutation in primary papillary cancers, in lymphonodal metastases at diagnosis and in recurrences; to value whether the BRAF mutation frequency is higher in relapsing cancers, particularly in those with no radioiodine uptake; 2) to determine whether the BRAF mutation is associated with increased glucose metabolism phenotypes. Patients and methods: 42 consecutive recurrences, belonging to 42 PTC affected patients who underwent surgery, were analysed. At the time of diagnosis they were subjected to thyroidectomy and to 131-I radioablation; then they were submitted to a total body scintigraphic examination 3 days after a 131-I therapeutic dose (2,7- 5,4GBq). 23/42 patients were submitted to a FDG-PET-CT examination as well. All the samples were paraffin ...