PAX8 Expression in Thyroid Tumors: Comparison with PAX2, TTF-1, and Thyroglobulin

Abstract

Objective: Diagnostic markers for thyroid differentiation remain in development. Paired box (PAX8) is a member of a transcription factor family instrumental for fetal development and probably neoplastic transformation of the kidney, müllerian organs, and thyroid. Expression of PAX8 in thyroid tissue is evaluated and compared with traditional thyroid markers which are thyroglobulin and thyroid transcription factor-1 (TTF-1). Materials and Methods: Consecutive tissue sections of non-neoplastic thyroid tissue ( n = 131), adenomatous nodule ( n = 26), follicular neoplasms ( n = 25), papillary carcinoma ( n = 13), medullary carcinoma ( n = 6), poorly differentiated carcinoma ( n = 16), undifferentiated carcinoma ( n = 6), and benign parathyroid tissue ( n = 15) were submitted for PAX8, PAX2, TTF-1, and thyroglobulin immunostain. Staining extent (% of cells stained) and intensity (score 0-3) were evaluated. Results: PAX2 was not seen in any specimens. Strong (intensity score 3) (and diffuse 100% of cells) nuclear staining for PAX8 was noted in every case of non-neoplastic thyroid tissue and differentiated thyroid tumors. Staining for TTF-1 was similar to that of PAX8 in term of frequency, but the extent and intensity were less for some variants of papillary carcinoma or less differentiated follicular neoplasms. Thyroglobulin was noted in every case of non-neoplastic thyroid tissue and differentiated thyroid tumors, but the staining (which is cytoplasmic) was weak and focal in 66 cases of them, and this staining was often masked by strong staining of the adjacent colloid. For undifferentiated carcinoma, PAX8 was the only expressed marker, but in only 1/6 cases. For medullary carcinoma, PAX8 was not seen in any case, but TTF-1 and thyroglobulin were noted in 67% and 33% of cases, respectively. For parathyroid tissue, PAX8 was noted in 80% of cases, but the staining was weak and focal in each; TTF-1 and thyroglobulin were not seen. Conclusions: (1) PAX8 is a very sensitive marker for thyroid differentiation, regardless of diagnoses, (2) PAX8 is the only available marker, albeit of limited sensitivity, for undifferentiated thyroid carcinoma, (3) Both PAX8 and TTF-1 are sensitive markers for thyroid differentiation; with a diagnostic advantage for PAX8; and both are superior to thyroglobulin, (4) PAX8 may be the only marker needed for evaluating thyroid differentiation, and (5) In spite of an ontogenic similarity with PAX8, PAX2 is not expressed by thyroid tissue.