Abstract: Objective To investigate the association between RET genotype and disease phenotype in the patients with hereditary medullary thyroid carcinoma (HMTC). Methods A total of 13 patients diagnosed as HMTC and undergoing surgical treatment for thyroid carcinoma in this hospital from March 2015 to September 2019 were analyzed retrospectively with follow-up cutoff at September 2021. The patient risk stratification was performed according to American Thyroid Association (ATA) guidelines. The association between RET genotype and disease phenotype including biochemical results, TNM stage, both biochemical [normal serum calcitonin(CT)] cure and clinical cure was analyzed. Results There were 1 (7.69%) case, 6(46.15%) cases, and 6(46.15%) cases with the highest risk mutation (RET M918T), high-risk mutation (RET C634Y and C634S), and moderate-risk mutation (RET C618G and C611Y), respectively. One case with the highest risk mutation was at TNM stage Ⅳ. There were 4 cases (66.67%) at stageⅠand 2 cases (33.33%) at stage Ⅲ among 6 cases with high-risk mutation. For 6 cases with moderate-risk mutation, stage Ⅰ and stage Ⅱ had 1 case(16.67%) respectively, and stage Ⅲ and stage Ⅳ with 3 cases (50%) and 1 case (16.67%) respectively. The highest preoperative CT and carcinoembryonic antigen were detected in 1 case with highest risk mutations (20 000 ng/L, 831.8 μg/L), and those lower in 6 cases with moderate-risk mutations (1 221.4 ng/L, 62.3 μg/L). The lowest of them were in 6 cases with high-risk mutations (537.7 ng/L, 41.7 μg/L). Similarly, both clinical cure rate and biochemical cure rate were found poorer in the cases with the highest risk mutation, and better in the case with high-risk mutation, and less better in the cases with moderate-risk mutation. Conclusions RET gene could be associated with HMTC risk of ATA. The patients of RET genotype with high-risk mutations would have higher clinical cure rate and biochemical cure rate than the cases with moderate-risk mutations.

Key words: Medullary thyroid carcinoma, Hereditary medullary thyroid carcinoma, Multiple endocrine neoplasia syndrome, RET gene