Virchows Archiv

, Volume 472, Issue 5, pp 779–787 | Cite as

In papillary thyroid carcinoma, expression by immunohistochemistry of BRAF V600E, PD-L1, and PD-1 is closely related

  • Yanhua Bai
  • Ting Guo
  • Xiaozheng Huang
  • Qi Wu
  • Dongfeng Niu
  • Xinqiang Ji
  • Qin Feng
  • Zhongwu Li
  • Kennichi Kakudo
Original Article


Immune checkpoint inhibitor therapies targeting PD-L1/PD-1 have been shown to be effective in treating several types of human cancer. In papillary thyroid carcinoma (PTC), little is known about the expression of PD-L1/PD-1 in the tumor microenvironment or its potential correlation with BRAF V600E mutation status. In this study, we examined the expression of PD-L1, PD-1, and BRAF V600E in PTC by immunohistochemistry and investigated the clinical significance of expression status. We studied the expression of PD-L1, PD-1, and BRAF V600E by immunohistochemical staining in 110 cases of PTC with a diameter > 1 cm. Cases with a background of chronic lymphocytic thyroiditis (CLT) were excluded, as differentiating lymphocytes in the context of CLT from tumor-infiltrating lymphocytes (TILs) is difficult. We classified PD-L1+/PD-1+ expression as type 1 (41%), PD-L1−/PD-1− as type 2 (17%), PD-L1+/PD-1− as type 3 (5%), and PD-L1−/PD-1+ as type 4 (37%). Significant correlations were found between expression of BRAF V600E and that of PD-L1 and PD-1. The positive correlation observed between expression of BRAF V600E and PD-L1/PD-1 suggests that immunotherapies targeting PD-L1/PD-1 might be effective for PTC patients with the BRAF V600E mutation, which are refractory to radioiodine therapy.


BRAF V600E PD-L1 PD-1 Papillary thyroid carcinoma Immunohistochemistry 


Author contributions

BY, GT, KK, and LZ conceived and designed the experiments. HX and WQ performed the experiments. BY and ND reviewed the slides; JX and FQ analyzed the data. BY and GT wrote the manuscript.


This work was supported by the National Nature Science Foundation of China (Nos. 81202114, 81301874, and 81301879), the National Science Foundation of Beijing (No. 7132051), and the General Program, Research Fund for the Doctoral Program of Higher Education (No. 2012001120135).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Yanhua Bai
    • 1
  • Ting Guo
    • 2
  • Xiaozheng Huang
    • 1
  • Qi Wu
    • 1
  • Dongfeng Niu
    • 1
  • Xinqiang Ji
    • 3
  • Qin Feng
    • 1
  • Zhongwu Li
    • 1
  • Kennichi Kakudo
    • 4
  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of PathologyPeking University Cancer Hospital & InstituteBeijingChina
  2. 2.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & InstituteBeijingChina
  3. 3.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical StatisticsPeking University Cancer Hospital & InstituteBeijingChina
  4. 4.Department of Pathology, Nara HospitalKindai University Faculty of MedicineIkomaJapan

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