Clinical and genomic characterization of sporadic medullary thyroid carcinoma in Chinese patients.

person Yang Liu Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China info_outline Yang Liu, Tingwei Lu, Xiaoyan Lin

Authors person Yang Liu Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China info_outline Yang Liu, Tingwei Lu, Xiaoyan Lin Organizations Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, China, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China Abstract Disclosures Research Funding No funding sources reported Background: Medullary thyroid carcinoma (MTC) is a C-cell-derived epithelial neuroendocrine neoplasm. MTC has a low prevalence and a relatively worse prognosis compared with differentiated thyroid carcinoma. About 75% of all MTCs are sporadic. The clinicogenomic landscape of sporadic medullary thyroid carcinoma (sMTC) in the Chinese population was rarely described. Methods: Formalin-fixed paraffin-embedded (FFPE) samples and/or tumor tissues from a total of 121 sMTC patients from 22 centers were retrospectively collected and tested using a targeted 28-gene next-generation sequencing (NGS) panel (May 2022 to November 2023). Clinicopathological data, including age, gender, histological diagnoses, site, tumor size, and status of the lymph nodes and distant metastasis were reviewed. Regression analyses were performed to examine the association between the clinicogenomic characterization and pathologic features. Results: A total of 105 out of 121 sMTC were NGS-positive. The mutant genes included RET(66.9%), RAS(20.7%), BRAF(1.6%), TSHR(0.8%). The top 5 frequent mutations were RET M918T (24.8%, 30/121), HRAS Q61R (8.3%, 10/121), RET C634R (7.4%, 9/121), RET V804M (4.1%, 5/121), HRAS Q61K (4.1%, 5/121). Of the 13 co-mutations, 12 were RET mutations or co-occurrence of RET with other genetic alterations. Besides, the higher the age, the lower the probability of lymph node metastasis (OR=0.95, p=0.005). Also, patients with common RET mutations (including M918T, C634, C630, C611, C618, C620, A883F, S891 and V804) tended to have lymph node metastases (OR=5.67, p=0.016). We observed a significant positive linear relationship (Beta=2.0) between other gene mutations (non-RET mutations and non-RAS mutations) and tumor size. However, when the tumor diameter was analyzed according to whether it was greater than 1cm, we found that clinical factors such as age, sex, and gene mutation were not related to tumor size. Moreover, we did not find any association between this cutoff value of tumor size and lymph node metastases. It indicated that sMTC clinical diagnosis and treatment may consider pathologic and genomic features, not just whether the tumor size is >1cm. Conclusions: Our study first provided the molecular characteristic of Chinese patients with large-scale sMTC. Analysis revealed that common RET mutations may be potential predictors of lymph node metastases. These conclusions remain to be validated in prospective large-scale cohorts.