Title : The association of gene mutation and neck lymph node metastasis in patients with medullary thyroid carcinoma

Background: Genetic mutations are closely associated with the development, risk stratification, and cervical lymph node metastasis of medullary thyroid carcinoma (MTC). Advances in sequencing technology enable a more precise investigation of the relationship between genetic mutations and cervical lymph node metastasis in MTC. This study aims to explore the role of genetic mutations in determining the cervical lymph node metastasis among patients with MTC by next-generation sequencing (NGS) technology.

Methods: Thirty patients with MTC, as confirmed by immunohistochemistry and pathology findings, were enrolled in the study. These patients had undergone thyroidectomy and neck lymph node dissection with lymph node metastasis. Second-generation sequencing was used to detect genetic alterations, including single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), in 425 genes, such as the RET gene. Further analysis examined the correlation between the site of lymph node metastasis (central or central and lateral neck lymph nodes) and RET mutations, as well as the association between different mutations and tumor burden.

Results: Among 30 MTC patients with lymph node metastasis, the overall RET mutation rate was 90% (27/30). Specifically, RET mutations were detected in all 23 patients with central and lateral neck lymph node metastasis. Among the 7 patients with central lymph node metastasis only, 4 exhibited RET mutations, yielding a RET mutation rate of 57.14%. Compared with MTC patients without RET mutations, the difference was statistically significant (P=0.0086). The p.M918T mutation was the most common, with a mutation rate of 42.86%, followed by p.C618R/G and p.C634Y.  Patients harboring specific site mutations (p.M918T or p.C618R/G) exhibited a higher incidence of lateral neck metastasis (P=0.0309).

Conclusion: RET gene mutations are associated with the risk of lateral neck lymph node metastasis in MTC patients, particularly the p.M918T mutation. The p.M918T or p.C618R/G mutations hold promise as potential predictors of lateral neck lymph node metastasis. Clinicians may find it valuable to consider prophylactic lateral neck lymph node dissection in MTC patients harboring these RET mutation types and negative lateral neck imaging evaluations.

Keywords: MTC; gene mutation; RET; cervical lymph node metastasis

Zheng Weihui is a clinician specializing in thyroid surgery. She holds an MD and completed postdoctoral training. She works as a master’s supervisor and specially appointed associate researcher, is awarded Young Healthcare Talent of Zhejiang Province, and has been a visiting scholar at Singapore’s A*STAR. Her practice covers thyroid and parathyroid surgery. Committed to addressing real-world surgical challenges, her research focuses on intraoperative recurrent laryngeal nerve preservation and parathyroid identification. She performs open and endoscopic operations with cosmetic incisions to facilitate rapid recovery, and explores novel multidisciplinary therapies for advanced thyroid malignancies.