No correlation between PD-L1 and NIS expression in lymph node metastatic papillary thyroid carcinoma

Background: About 90% of thyroid cancers originate from follicular epithelial cells as differentiated thyroid cancer (DTC). 90% of DTC is papillary thyroid cancer (PTC), 10% is follicular thyroid cancer (FTC). The standard of care for PTC is surgery followed by radioiodine (RAI) ablation and thyroid stimulating hormone (TSH) suppressive therapy. The treatment of radioiodine refracter DTC is challenging. While during malignant transformation thyroid epithelial cells lose their ability to accumulate radioiodine (due to impaired membrane targeting or lacking NIS expression), it has recently been reported that PD-L1 expression in thyroid cancer cells increases during dedifferentiation. Since NIS and PD-L1 expression has never been investigated together in thyroid cancer, the aim of our present study was to investigate and correlate PD-L1 and NIS expression in the same primary tumor samples of lymph node metastatic PTC. Methods: The expression of hNIS (human natrium/sodium iodide symporter) and PD-L1 was studied by immunohistochemistry analyses in primary tumor samples of metastatic PTC patients. Results: PD-L1 and NIS immunohistochemistry analysis was performed in 89 and 86 PTC cases, respectively. 25 tumors did not show PDL1 expression, while in 58 tumors, 1-50% of the tumor cells showed PD-L1 expression, and in 6 tumors more than 50% of the cells were positive for PD-L1. NIS immunohistochemistry was performed on 86 primary papillary carcinomas. 51 out of 86 tumors showed NIS expression, only in 7 cases NIS was localized in the plasma membrane, while in most tumors NIS was retained in the intracytoplasmic membrane compartments. Conclusion: No correlation was found between PD-L1 and NIS expression. It is tempting to speculate whether manipulation of the PD1/PDL1 axis by anti-PDL1 or anti-PD1 antibodies, could restore NIS functional expression. Based on the present study we can only conclude that the percentage of NIS expressing or PD-L1 expressing tumor cells does not correlate in the primary tumor of lymph node metastatic PTC.