EP39 – Is PD-L1 expression an epiphenomenon in papillary thyroid cancer?

      Fookerah, Prishila2; Perampalam, Sumathy1,6;  Ali, Sayed3,6; Shadbolt, Bruce4,6; Fadia, Mitali5,6 1 Department of Endocrinology, Canberra Hopsital, ACT Australia 2 Department of Medicine, Canberra Hospital, ACT, Australia 3 Department of Oncology, Canberra hospital, ACT, Australia 4 Department of Clinical Epidemiology, Biostatistics and Data Science Canberra Hospital, ACT, Australia 5 Department of Pathology, Canberra Hospital, ACT, Austrlia 6 Medical School, Australian National University, ACT, Australia   Background: The impact of the immune system on disease progression in papillary thyroid cancer (PTC) is poorly understood. PD-L1 expression as a predictor of disease progression has been explored recently with PD-L1 positivity in PTC ranging between 6.1% and 82.5%.However PD-L1 expression may be altered in PTC with concurrent lymphocytic thyroiditis (LT), which has not been accounted for consistently in previous studies (1-5).  Aim: To determine if lymphocytic thyroiditis has an effect on  PD-L1 expression in PTC. Method: A cross sectional study was performed, analysing PTC patients diagnosed from 2005-2012. Immunohistochemistry analysis of archived formalin fixed paraffin embedded thyroid tissues for PD-L1 expression using a rabbit monoclonal anti-PD-L1 antibody (Ventana SP263) was performed. The expression of membranous PD-L1 in thyroid was considered positive and  intensity of the staining was scored. The results were classified according to the AJCC TNM staging system comparing samples with and without LT. Chi-square tests were performed for statistical analysis. Results: The study cohort consisted of 69 PTC cases with 21 (30.4%)cases of  LT. Expression of PD-L1 in tumour cells was  present in 8(38%) cases with LT and  2 cases (4.1%)  without LT (Chi Square =13.6; p=0.0002) . There was no difference in positivity across the TNM stages. High intensity expression of PD-L1 was seen in PTC at lower stage disease with concurrent LT.  In LT without PTC, PD-L1 expression was absent in thyroid, but present in lymphocytes. Conclusion: Frequency of PD-L1 expression was significantly higher in PTC with LT than PTC without LT. PD-L1 expression in PTC may be an epiphenomenon and future studies should account for presence of concurrent LT.   References:
    1. Angell, T.E.  et al BRAFV600E in Papillary Thyroid Carcinoma Is Associated with Increased Programmed Death Ligand 1 Expression and Suppressive Immune Cell Infiltration Thyroid Volume 24, Number 9, 2014
    2. Cunha, Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation Endocrine-Related Cancer (2013) 20, 103–110
    3. Chowdhury, PDL-1 overexpression is a prognostic marker for aggressivepapillary thyroid cancer and its variants. Oncotarget 2016 (7); 22.
    4. Ahn et al ; Comprehensive screening of PDL1 expression in thyroid cancer; Endocrine-Related Cancer (2017) 24, 97–106
    5. She, R.L. Programmed Death-Ligand 1 Expression in Papillary Thyroid Cancer and Its Correlation with Clinicopathologic Factors and Recurrence Thyroid Volume X, Number X, 201X


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