Endocrine Abstracts

JOINT2320

This is a single-center study of 106 subjects who were tested for germline RET mutations at our center. Among those, 97 were diagnosed with MTC and 9 had genetically positive family history and underwent screening. A total of 74 patients underwent complete RET gene testing on exons 5, 8, 10, 11, 13, 14, 15, 16 and on the rest of 32 patients targeted analysis was performed. We identified a germline RET variant in 40 of 106 (37.7%) patients from 9 families; 8/40 (20%) were initially considered sporadic cases based on the negative family history for MTC or MEN2 related pathologies and from the 32 patients with positive family history, 9 were index cases and 23 relatives. Considering the identified mutations, when classified in ATA risk categories, 20/40 (50%) patients harboured a “high risk” (H) level mutation and 20/40 a “moderate risk” (MOD) level mutation. ATA H risk RET mutations: 20/20 (100%) with C634Trp/Phe/Arg mutations; 15/20 (75%) patients underwent thyroid surgery and were dignosed with MTC. Median (min-max) age at surgery was 37.4 (21-56) years. ATA MOD risk RET mutations: 8/20 (40%) patients with C618Arg mutation, 8/20 (40%) patients with C620Arg mutation and 4/20 (20%) with V804Met mutation; 16/20 (80%) patients had total tiroidectomy with median age (min-max) at surgery of 36 (10-68) years. As for genotype-phenotype correlation in MEN2 syndrome, 10/20 (50%) patients with a codon 634 mutation and 4/8 (50%) with a codon 618 mutation presented PHEO; in our cohort, no patient with codon 620 and 804 presented PHEO until the end of follow-up. Of all PHEO patients, 6/14 (42.8%) had bilateral disease with the median age of 9.6 years between left and right disease. Primary hyperparathyroidism (HPTH) was diagnosed in 6/20 patients, all with mutation in codon 634 and the median age was 43 years. Out of 66 cases tested negative for germline RET mutation, ten cases with advanced, metastatic MTC underwent RET somatic testing using fresh or formalin-fixed, paraffin-embedded primary tumor/metastasis tissue. From them, 8/10 (80%) patients tested positive for Met918Thr mutation and two cases harbored Cys634Arg mutation. Mutational screening is mandatory in all patients with extended MTC, being crucial in selecting targeted treatment with TKI inhibitors and predicting responsiveness to therapy.