Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms

Abstract

Thyroid-specific transcription factors, Pax8, TTF-1, and TTF-2, are crucial for thyroid organogenesis and differentiation. Compared with TTF-1, the other two markers have scarcely been investigated in surgical pathology. The goal of this study is to evaluate the expressions of these markers in thyroid tumors of the full spectrum of differentiation, with special emphasis on anaplastic carcinomas. A total of 94 cases of thyroid neoplasms were studied: 17 papillary carcinomas, 18 follicular adenomas, 16 follicular carcinomas, 7 poorly differentiated carcinomas, 28 anaplastic carcinomas, and 8 medullary carcinomas. Immunostains for these three markers were performed. The antibodies to Pax8 and TTF-2 were also applied on 147 lung carcinomas as well as a variety of normal tissues and malignant tumors. All three markers were seen in papillary carcinomas, follicular adenomas and carcinomas, and poorly differentiated carcinomas in a diffuse manner, whereas their expressions in medullary carcinomas were variable. Pax8 was expressed in 79% of anaplastic carcinomas to a variable extent, whereas TTF-1 and TTF-2 were seen only in 18 and 7% of anaplastic carcinomas, respectively. TTF-2 was negative in all other neoplastic and non-neoplastic tissues including those of the lung. Pax8 was expressed in renal tubules, fallopian tubes, ovarian inclusion cysts, and lymphoid follicles as well as renal carcinoma, nephroblastoma, seminoma, and ovarian carcinoma, but not in normal tissue and carcinomas of the lung. Pax8 is a useful marker for the diagnosis of anaplastic carcinomas, particularly when the differential diagnosis includes pulmonary carcinoma. In differentiated thyroid neoplasms, no significant difference in expression was seen in all the three transcription factors.

Pleomorphic mesothelioma: report of 10 cases

“…Another type of carcinoma with which pleomorphic mesotheliomas can potentially be confused is anaplastic thyroid carcinoma, as these tumors frequently metastasize to the lung and may involve the pleura. As in the case of pleomorphic carcinomas of the lung, anaplastic thyroid carcinomas do not express calretinin, mesothelin or WT1, but can express Pax8, 23,24 a marker that is absent in mesotheliomas. 25 TTF-1 has little value as it has been reported to be expressed only in a small percentage of anaplastic thyroid carcinomas.…”

“…25 TTF-1 has little value as it has been reported to be expressed only in a small percentage of anaplastic thyroid carcinomas. 23,26 Pleomorphic mesotheliomas can also be confused with some sarcomas. The two sarcomas with the greatest potential of being confused with pleomorphic mesotheliomas are angiosarcomas and the pleomorphic variant of malignant fibrous histiocytoma.…”

PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study

“…It may also mediate neoplastic transformation as 15 PAX 8-PPARg rearrangement occurs in 20-30% of follicular thyroid carcinomas. [12][13][14][15] PAX 8, together with PAX 2 and PAX 5, controls lymphoid genesis, especially the maturation of B cells. 26 …”

“…A few limited studies have identified PAX 8 in neoplasms of the organs the embryogenesis of which is under control of this transcription factor, including thyroid follicular neoplasm, [12][13][14][15] renal cell carcinoma, 11,16 nephrogenic adenoma, 17 and ovarian carcinoma. [18][19][20] Confirmation of PAX 8 as a sensitive marker for these tumor types is required.…”

PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma

“…[14][15][16] Although PAX8 has been most studied in renal tissues and neoplasms, 17 it has been recently recognized as a useful marker in distinguishing ovarian from breast carcinoma, 18 and as a marker of thyroid epithelial neoplasms. 19 Moreover, our group recently observed intense PAX8 reactivity in pancreatic neuroendocrine tumors and normal pancreatic islets in a large tissue microarray evaluation of PAX8 immunoreactivity of non-renal tissues/neoplasms. 20 Very little is known about the role of PAX8 in endocrine cell development, and differential PAX8 expression in neuroendocrine tumors of the pancreas, gastrointestinal tract, and lung could be of potential clinical utility.…”