PD-L1 expression and Ki-67 index may play important roles in medullary thyroid carcinoma (MTC), suggesting a possible shift in immunotherapy targets and prognostic tools, according to a study recently published in Virchows Archiv.

“Most importantly, we noted that PD-L1 expression was significantly correlated with HRAS mutations, which indicated that patients with HRAS mutations were more likely to benefit from immunotherapy targeting PD-L1/PD-1,” the authors wrote.

This experimental study included samples from 49 patients with sporadic MTC obtained during surgical resection of the tumor. Immunohistochemistry and next-generation sequencing determined the expression of PD-L1, Ki-67 index, and genetic alterations to later analyze the association between them. 

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An important finding was that the tumors that expressed PD-L1 were also negative for the RET M918T mutation while exhibiting a positive correlation with HRAS mutations. This result indicates a novel therapeutic target to be explored for cases with such genotypes.

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On the other hand, the Ki-67 index was not associated with major genetic alterations. In addition, PD-L1 expression and the Ki-67 index did not show any correlation.

Regardless, a Ki-67 index above 2% was associated with poor disease-free survival. Likewise, the presence of the RET M918T mutation also seemed to coincide with worse outcomes.

“We identified that the Ki-67 index and RET M918T mutation, but not PD-L1, were useful predictors for tumor recurrence,” Bai et al said.

These results may pinpoint novel uses for the Ki-67 index and PD-L1 expression in patients with MTC. Determining both characteristics involves immunohistochemistry studies on the tumor biopsy. 

For example, the Ki-67 index of a patient could help predict the risks of disease-free survival and tumor relapse, hence promoting a personalized therapeutic scheme and follow-up of each patient after surgery. Although this study reports that RET mutations could also serve this purpose, the patient would have to undergo further genetic testing, which could be costly and may not always be available.


Bai Y, Guo T, Niu D, et al. Clinical significance and interrelations of PD-L1 expression, Ki-67 index, and molecular alterations in sporadic medullary thyroid carcinoma from a Chinese population. Virchows Arch. Published online August 3, 2022. doi:10.1007/s00428-022-03390-9