Background: Treatment options for poorly differentiated (PDTC) and anaplastic (ATC)
thyroid carcinoma are unsatisfactory and prognosis is generally poor. Lenvatinib (LEN), a
multi-tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR) 1-4 is
approved for advanced radioiodine refractory thyroid carcinoma, but response to single
agent is poor in ATC. Recent reports of combining LEN with PD-1 inhibitor
pembrolizumab (PEM) are promising.
Materials and Methods: Primary ATC (n=93) and PDTC (n=47) tissue samples
diagnosed 1997-2019 at five German tertiary care centers were assessed for PD-L1
expression by immunohistochemistry using Tumor Proportion Score (TPS). FGFR 1-4
mRNA was quantified in 31 ATC and 14 PDTC with RNAscope in-situ hybridization.
Normal thyroid tissue (NT) and papillary thyroid carcinoma (PTC) served as controls.
Disease specific survival (DSS) was the primary outcome variable.
Results: PD-L1 TPS≥50% was observed in 42% of ATC and 26% of PDTC specimens.
Mean PD-L1 expression was significantly higher in ATC (TPS 30%) than in PDTC (5%;
p<0.01) and NT (0%, p<0.001). 53% of PDTC samples had PD-L1 expression ≤5%.
FGFR mRNA expression was generally low in all samples but combined FGFR1-4
expression was significantly higher in PDTC and ATC compared to NT (each p<0.001).
No impact of PD-L1 and FGFR 1-4 expression was observed on DSS.
Conclusion: High tumoral expression of PD-L1 in a large proportion of ATCs and a
subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR
expression is low thyroid tumor cells. The clinically observed synergism of PEM with
LEN may be caused by immune modulation.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84554 |
| Date | 04 April 2023 |
| Creators | Adam, Pia, Kircher, Stefan, Sbiera, Iuliu, Koehler, Viktoria Florentine, Berg, Elke, Knösel, Thomas, Sandner, Benjamin, Fenske, Wiebke Kristin, Bläker, Hendrik, Smaxwil, Constantin, Zielke, Andreas, Sipos, Bence, Allelein, Stephanie, Schott, Matthias, Dierks, Christine, Spitzweg, Christine, Fassnacht, Martin, Kroiss, Matthias |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-2392, 712107 |
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