Clinical significance and interrelations of PD-L1 expression, Ki-67 index, and molecular alterations in sporadic medullary thyroid carcinoma from a Chinese population

Immunotherapy shows prospects in treating advanced medullary thyroid carcinoma although controversial reports are present. Recently, histological grading has been applied to medullary thyroid carcinoma by the Ki-67 index, mitotic figures, and tumor necrosis. However, the interrelation of PD-L1 expression, the Ki-67 index, and major genetic alterations of sporadic medullary thyroid carcinoma has not been fully reported. We examined the expression of PD-L1 (SP142 and 22C3) and the Ki-67 index immunohistologically and detected the major genetic alterations by next-generation sequencing in a cohort of sporadic medullary thyroid carcinomas, studied their survival impact, and discussed their interrelation. We identified that a high Ki-67 index (> 2%) and positive RET M918T mutation were correlated with poor disease-free survival but were not correlated with PD-L1 expression. All PD-L1 positive tumors were RET M918T mutation negative, and PD-L1 expression was positively correlated with HRAS mutation. The Ki-67 index was correlated with neither PD-L1 expression nor major genetic alterations. Our results indicate that immunotherapy targeting PD-L1/PD-1 might be more effective for patients with sporadic medullary thyroid carcinoma harboring HRAS mutations.