A study of FoxA1 expression in thyroid tumors.

FoxA1 regulates a variety of tissues during embryogenesis and early life. In thyroid, FoxA1 expression has recently been shown in C cells and medullary thyroid carcinomas but not in follicular cells. FoxA1 has also been proposed as a potential oncogene in anaplastic thyroid carcinomas. However, FoxA1 expression has not been extensively investigated in a spectrum of thyroid nonneoplastic lesions and tumors. A variety of thyroid tumors and lesions and their morphologic mimics were stained with monoclonal anti-FoxA1 antibody. For the medullary carcinomas, its expression pattern was compared with those of other conventional markers. All 67 medullary thyroid carcinomas (100%), including 1 calcitonin-negative medullary carcinoma, showed diffuse and strong FoxA1 nuclear expression. The expression pattern was homogeneous throughout the tumor. Expressions of other markers in medullary thyroid carcinomas were as follows: calcitonin, 94.7%; CEA, 91.2%; and chromogranin, 100%, generally in variable intensity. FoxA1 was completely negative in follicular neoplasms, papillary thyroid carcinomas, and poorly differentiated carcinomas, whereas it was expressed in 55% of anaplastic thyroid carcinomas (33/60) in variable intensity. FoxA1 was also strongly expressed in C-cell hyperplasia as well as solid cell nests. No FoxA1 expression was seen in thyroid gland affected by nodular hyperplasia, Hashimoto thyroiditis, and Graves disease, or in paragangliomas or parathyroid lesions. FoxA1 discriminates between medullary thyroid carcinoma and tumors of follicular derivation with sensitivity and specificity greater than calcitonin and CEA; therefore, it may serve as a reliable ancillary marker for the diagnosis of medullary thyroid carcinoma because of its reliably uniform quality of staining.