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

Mod Pathol. 2008 Feb;21(2):192-200. doi: 10.1038/modpathol.3801002. Epub 2007 Dec 14.


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.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma, Follicular / diagnosis
  • Adenocarcinoma, Follicular / metabolism
  • Adenoma / diagnosis
  • Adenoma / metabolism*
  • Adenosine Triphosphatases / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Calcitonin / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / metabolism
  • Carcinoma, Medullary / diagnosis
  • Carcinoma, Medullary / metabolism
  • Carcinoma, Papillary / diagnosis
  • Carcinoma, Papillary / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Hyperplasia
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / metabolism*
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / metabolism*
  • Tissue Array Analysis
  • Transcription Factors / metabolism*


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • Transcription Factors
  • Calcitonin
  • Adenosine Triphosphatases
  • TTF2 protein, human