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      Programmed death ligand 1 (PD-L1) expression in parathyroid tumors

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          Abstract

          Introduction

          PD-L1 is associated with prognosis and immunotherapeutic response in patients with malignancies. In previous studies, PD-L1 expression was detected in many endocrine tumors. However, the PD-L1 expression status in parathyroid tumors is unknown.

          Methods

          We included 26 parathyroid carcinoma and 37 adenoma samples, as well as the corresponding patient information. PD-L1 was stained using the FDA-approved PD-L1 IHC 22C3 pharmDx and Ventana PD-L1 (SP263) assays, and staining was assessed by the estimated percentages of positive tumor cells and immune cells, respectively.

          Results

          We classified the PD-L1 expression in the parathyroid tumors into four groups: (0) <1%, (1) 1–4%, (2) 5–9% and (3) ≥10% positive. With the SP263 clone, 37 (carcinoma:adenoma = 18:19) samples scored 0, 13 (carcinoma:adenoma = 4:9) scored 1, 7 (carcinoma:adenoma = 1:6) scored 2 and 6 (carcinoma:adenoma = 3:3) scored 3. However, in the series of cases using the 22C3 clone, 45 (carcinoma:adenoma = 20:25) samples scored 0, 10 (carcinoma: adenoma = 3:7) scored 1, 5 (carcinoma:adenoma = 1:4) scored 2, and 3 (carcinoma:adenoma = 2:1) scored 3. Concerning tumor-infiltrating immune cells, 57 samples were negative and six were positive with SP263, and 59 were negative and four were positive with 22C3. Moreover, PD-L1 expression was negatively correlated with the Ki-67 index and mitotic rate in parathyroid tumors depending on the different clones. However, the results indicated only moderate consistency between the SP263 and 22C3 clones in parathyroid tumors.

          Conclusion

          We found deficient PD-L1 expression in the majority of parathyroid tumors. However, the PD-L1 expression score in parathyroid tumors depended greatly on the antibody clone used.

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          Most cited references15

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          Trends in the incidence and treatment of parathyroid cancer in the United States.

          Parathyroid cancer is a rare cause of hyperparathyroidism. The objectives of this study were to determine the patterns of disease, treatment trends, and outcomes among patients with parathyroid cancer by using a population-based data source. Surveillance, Epidemiology, and End Results (SEER) cancer registry data were used to identify patients who were diagnosed with parathyroid cancer from 1988 through 2003. To assess whether the incidence rate, treatment, tumor size, and cancer stage changed over time, the Cochrane-Armitage trend test was used, and Cox proportional-hazards modeling was used to identify the factors associated with an improved overall survival rate. From 1988 through 2003, 224 patients with parathyroid cancer were reported in the SEER data. Over that 16-year study period, the incidence of parathyroid cancer increased by 60% (1988-1991, 3.58 per 10,000,000 population; 2000-2003, 5.73 per 10,000,000 population). Most patients (96%) underwent surgery (parathyroidectomy, 78.6% of patients; en bloc resection, 12.5% of patients; other, 4.9% of patients). The rate of surgical treatment increased significantly during the study period. The 10-year all-cause mortality rate was 33.2%, and the 10-year cancer-related mortality rate was 12.4%. Patient age (P<.0001), sex (P=.0106), the presence of distant metastases at diagnosis (P=.0004), and the year of diagnosis (P=.0287) were associated significantly with the overall survival rate. Tumor size, lymph node status, and type of surgery were not associated significantly with the overall survival rate. Although parathyroid cancer is rare, the incidence increased significantly in the United States from 1988 through 2003. Young age, female gender, recent year of diagnosis, and absence of distant metastases were associated significantly with an improved survival rate. Copyright (c) 2007 American Cancer Society
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            Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants

            Programmed death-ligand 1(PD-L1) expression on tumor cells is emerging as a potential predictive biomarker in anti-PD-L1 directed cancer immunotherapy. We analyzed PD-L1 expression in papillary thyroid carcinoma (PTC) and its variants and determined its prognostic potential to predict clinical outcome in these patients. This study was conducted at an academic oncology hospital which is a prime referral centre for thyroid diseases. Immunohistochemical subcellular localization (IHC) analyses of PD-L1 protein was retrospectively performed on 251 archived formalin fixed and paraffin embedded (FFPE) surgical tissues (66 benign thyroid nodules and 185 PTCs) using a rabbit monoclonal anti-PD-L1 antibody (E1L3N, Cell Signaling Technology) and detected using VECTASTAIN rapid protocol with diaminobenzidine (DAB) as the chromogen. The clinical-pathological factors and disease outcome over 190 months were assessed; immunohistochemical subcellular localization of PD-L1 was correlated with disease free survival (DFS) using Kaplan Meier survival and Cox multivariate regression analysis. Increased PD-L1 immunostaining was predominantly localized in cytoplasm and occasionally in plasma membrane of tumor cells. Among all combined stages of PTC, patients with increased PD-L1 membrane or cytoplasmic positivity had significantly shorter median DFS (36 months and 49 months respectively) as compared to those with PD-L1 negative tumors (DFS, both 186 months with p < 0.001 and p < 0.01 respectively). Comparison of PD-L1+ and PD-L1− patients with matched staging showed increased cytoplasmic positivity in all four stages of PTC that correlated with a greater risk of recurrence and a poor prognosis, but increased membrane positivity significantly correlated with a greater risk of metastasis or death only in Stage IV patients. In conclusion, PD-L1 positive expression in PTC correlates with a greater risk of recurrence and shortened disease free survival supporting its potential application as a prognostic marker for PTC.
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              Total mutation burden (TMB) in lung cancer (LC) and relationship with response to PD-1/PD-L1 targeted therapies.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                July 2019
                06 June 2019
                : 8
                : 7
                : 887-897
                Affiliations
                [1 ]Department of Pathology , Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                [2 ]Clinical Biobank , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                [3 ]Department of General Surgery , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
                Author notes
                Correspondence should be addressed to J Sun or Z Liang: sunjian0720@ 123456126.com or liangzhiyong1220@ 123456yahoo.com
                Article
                EC-19-0163
                10.1530/EC-19-0163
                6599073
                31252398
                1cb12c88-1aff-4b1f-9c98-003522764142
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 16 May 2019
                : 06 June 2019
                Categories
                Research

                pd-l1,parathyroid carcinoma,parathyroid adenoma,sp263,22c3
                pd-l1, parathyroid carcinoma, parathyroid adenoma, sp263, 22c3

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