Assessment of phenotypes in a unique group of RET proto-oncogene Y791F variant carriers in the Polish population

INTRODUCTION: Among all RET proto-oncogene variants, Y791F has been the most controversial and widely debated with regard to itspathogenicity and clinical significance. MATERIAL AND METHODS: Medical records of 104 RET Y791F variant carriers were retrospectively analyzed. The population comprised 30 probands with medullary thyroid carcinoma (MTC), 6 probands with pheochromocytoma, 63 family members, and 5 patients in whomthe RET Y791F variant was found during genetic screening. The characteristics of the 30 RET Y791F carriers with MTC were comparedwith those of the control group of 208 patients with sporadic MTC. RESULTS: The median age at surgery in the 30 probands with MTC was 58 years (range: 20-79), and in the control group with sporadic MTC it was 55 years (range: 21-80), with no statistically significant difference (p = 0.16). Multifocal MTC was observed in 8 of 30 operatedprobands (26%) and in 29 of 208 patients (13.9%) with sporadic disease (p = 0.07). Prophylactic surgery was performed in 21 familymembers. No MTC was identified in the postoperative material. Among patients under surveillance, none of the RET Y791F carriersshowed any abnormalities on thyroid ultrasound or any increase in calcitonin concentration. None of the followed-up patients (except 6after adrenalectomy) was diagnosed with pheochromocytoma. None of the 104 RET Y791F carriers had hypercalcemia. CONCLUSIONS: Based on our results, individuals with the RET Y791F variant do not require enhanced clinical surveillance or prophylactic intervention and should be managed according to general population guidelines, unless additional clinical indications arise.