Aberrant expression of CD20 in thyroid cancer and its clinicopathologic significance

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. BRAF^V600E 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 BRAF^V600E 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.