PD-L1 expression in papillary thyroid cancer with and without lymphocytic thyroiditis: a cross sectional study

Fadia, Mitali; Fookeerah, Prishila; Ali, Sayed; Shadbolt, Bruce; Greenaway, TM; Perampalam, Sumathy

doi:10.1016/j.pathol.2019.11.007

Cited by 12 publications

(11 citation statements)

References 14 publications

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“…The incidence and intensity of ICP expression were significantly higher in ATC than in WDTC ( 31 ). For example, the PDL1-positive rate in ATC, PDTC, and PTC was 64%, 32%, and 10%, respectively, which was consistent with previous studies ( 32 – 35 ).…”

Section: Discussionsupporting

confidence: 92%

Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma

et al. 2022

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BackgroundPatients with advanced thyroid carcinoma (TC), such as anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), and locally advanced papillary thyroid carcinoma (PTC), have poor prognoses and require novel treatments. Immune checkpoint (ICP) inhibitors have demonstrated encouraging and good results; nevertheless, their effect in advanced TCs remains largely unclear. Thus, we demonstrated ICP profiles and investigated their potential clinical significance.MethodsA total of 234 TC patients were involved, with 22 ATCs, 44 PDTCs, and 168 PTCs, including 58 advanced PTCs. Immunohistochemistry was performed to evaluate nine ICPs [programmed cell death ligand 1 (PDL1), Programmed cell death 1 (PD1), cytotoxic T lymphocyte-associated protein 4 (CTLA4), B and T lymphocyte attenuator (BTLA), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), lymphocyte activation gene 3 (LAG3), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B7 homolog 3 (B7-H3), and T-cell immunoglobulin and mucin domain- 3 protein (TIM3)] expression via tissue microarrays (TMAs), and clinical correlations were analyzed simultaneously.ResultsATC had the highest positive rate of ICPs among the three pathological types, as well as relatively high ICP co-expression. ATC with high expression of PDL1 positivity had a poor prognosis. Shorter survival was associated with VISTA, B7H3, TIM3, and TIGIT expression in PDTC. The greater the co-expression of these four ICPs, the poorer the prognosis in PDTC patients. VISTA and B7H3 were the two most commonly expressed ICPs in advanced PTC, both of which were linked to a poor prognosis.ConclusionsPDL1 is linked to the overall survival (OS) of ATC. A subset of PDTC is likely immunogenic with poor prognosis and co-expression of VISTA, B7H3, TIM3, and TIGIT. Furthermore, VISTA and B7H3 are prognostic biomarkers in advanced PTC. Single or combined blockade targeting these ICPs might be effective for advanced TCs in the future.

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Section: Discussionsupporting

confidence: 92%

Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma

et al. 2022

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“…PD-L1 expression has been reported for PTC tissue with and without lymphoid thyroiditis. PTC specimens with lymphoid thyroiditis showed higher expression of PD-L1 (39,1%) in comparison to PTC tissue without lymphoid thyroiditis (6,9%) ( 31 ). A review on the expression of PD-L1 in PTC tissue demonstrated significant association of PD-L1 expression with reduced disease-free survival (DFS), but not OS ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale

et al. 2021

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BackgroundTreatment 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 MethodsPrimary 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.ResultsPD-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.ConclusionHigh 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.

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“…Unfortunately, there is no consistency in defining HT and chronic lymphocytic thyroiditis in the studies, and thus, the comparison of the results is limited. Furthermore, also PD‐L1 analyses in HT cases faced methodological discrepancies, namely membranous vs. cytoplasmic expression, tumoral vs. tumoral and inflammatory expression, cutoffs of intensity and extent of immunopositivity [25]. In our study, only HT cases were included with strict diagnostic criteria and in 29.8% of cases, there was no epithelial PD‐L1 positivity in epithelium adjacent to inflammatory infiltrate including 28.6% of PTC cases and 21.4% of FED cases.…”

Section: Discussionmentioning

confidence: 99%

“…Of interest, several studies have reported the PD-L1/PD-1 expression in thyroiditis-related normal thyroid epithelium [22][23][24][25][26]. Lubin et al [23] showed PD-L1 expression up to 90% in HT epithelium, but only 1-5% in chronic lymphocytic epithelium.…”

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PD‐L1 and PD‐1 expression in thyroid follicular epithelial dysplasia: Hashimoto thyroiditis related atypia and potential papillary carcinoma precursor

Pakkanen

Kalfeřt

Ahtiainen³

et al. 2022

APMIS

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Programmed cell death ligand (PD-L1)/PD-1 expression has been studied in a variety of cancers and blockage of PD-L1/PD-1 pathway is a cornerstone of immunotherapy. We studied PD-L1/PD-1 immunohistochemical expression in 47 thyroid gland specimens in groups of (1) Hashimoto thyroiditis (HT) only; (2) HT and follicular epithelial dysplasia (FED); and (3) HT, FED, and papillary thyroid carcinoma (PTC). PD-1 positivity was found in immune cells, namely in lymphocytes, macrophages, and plasma cells with mean values for lymphocytes and macrophages 9% in HT group, 4% in FED group, and 4% in PTC group. PD-L1 positivity was identified in both immune cells and in the normal epithelial cells. In the HT group, mean PD-L1 staining on immune cells was 6%, in FED group 5%, and in PTC group 7%. The mean PD-L1 staining on the epithelial cells in the inflammatory parenchyma was 11.7% in HT, 13.4% in FED, and 8.3% in PTC group. The mean PD-L1 staining of FED foci was 47.2% in FED group and 33.6% in PTC group. The mean tumor proportion score (TPS) was 10.4%, and the mean combined positive score (CPS) was 15.5. At the moment, PTC is not a target of immunotherapy. However, understanding the complex issue of concurrent inflammation and autoimmunity can importantly influence the cancer treatment in future.

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PD-L1 expression in papillary thyroid cancer with and without lymphocytic thyroiditis: a cross sectional study

Cited by 12 publications

References 14 publications

Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma

Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma

FGF-Receptors and PD-L1 in Anaplastic and Poorly Differentiated Thyroid Cancer: Evaluation of the Preclinical Rationale

PD‐L1 and PD‐1 expression in thyroid follicular epithelial dysplasia: Hashimoto thyroiditis related atypia and potential papillary carcinoma precursor

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