Aberrant expression of CD20 in thyroid cancer and its clinicopathologic significance

Hum Pathol. 2018 Jan:71:74-83. doi: 10.1016/j.humpath.2017.10.015. Epub 2017 Oct 24.

Abstract

CD20 is the first-line diagnostic marker of B-cells, which serves as the target of the therapeutic monoclonal antibodies in B-cell lymphomas and leukemias. Recently, aberrant CD20 expression has been described in a small series of papillary thyroid carcinomas (PTCs). We aimed to evaluate CD20 immunoexpression and to perform clinicopathologic correlation in a large set of thyroid tumors, including a cohort of high-grade thyroid cancer. A total of 625 cases of thyroid tumor comprised tissue microarrays of 538 PTCs and 47 follicular adenomas, and whole-slide sections of 40 aggressive thyroid carcinomas (10 radioiodine-refractory PTCs and 8 poorly differentiated, 5 anaplastic, and 17 medullary thyroid carcinomas) were immunostained with anti-CD20 monoclonal antibody. BRAFV600E mutation was tested by direct sequencing in 478 cancers. Our study found that a small subset of PTCs (<10%, mainly of classic variant) exhibited aberrant membranous expression of CD20. These tumors displayed less aggressive histological features and had a lower prevalence of BRAFV600E mutation. We also discovered that CD20 expression was maintained in 6%-20% of aggressive thyroid cancers but not observed in follicular adenomas. All CD20-positive tumor cells were negative for CD79a and PAX5. Aberrant expression of CD20 by thyroid cancer cells may present a diagnostic pitfall in cytologic evaluation of thyroid and cervical masses. Residual expression of CD20 in aggressive cancers may offer promise for translational implications, which merits further experimental investigation.

Keywords: BRAF mutation; CD20; Immunohistochemistry; Papillary thyroid carcinoma; Thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / pathology
  • Adult
  • Antigens, CD20 / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*

Substances

  • Antigens, CD20
  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Supplementary concepts

  • Thyroid cancer, medullary