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

Mod Pathol. 2011 Jun;24(6):751-64. doi: 10.1038/modpathol.2011.3. Epub 2011 Feb 11.


PAX 8 is a transcription factor that is essential for embryonic development of the kidney, Müllerian organs, and thyroid. It may also have a role in tumor development in these organs. The diagnostic utility of PAX 8 has not been comprehensively studied. Formalin-fixed, paraffin-embedded tissue samples for non-neoplastic tissues (n=1601), primary neoplasms (n=933), and metastatic neoplasms (n=496) were subjected to PAX 8 immunostain. In non-neoplastic tissues, PAX 8 was consistently noted in glomerular parietal epithelial cells, renal collecting ductal cells, atrophic renal tubular epithelial cells regardless of nephronic segments, and epithelial cells of the endocervix, endometrium, fallopian tube, seminal vesicle, epidydimis, thyroid, pancreatic islet cells, and lymphoid cells. PAX 8 was not seen in the rest of the tissue samples. In primary neoplasms, PAX 8 was expressed by 194 of 240 (89%) renal cell neoplasms, by 238 of 267 (89%) Müllerian-type neoplasms, by 65 of 65 (100%) thyroid follicular cell neoplasms, by 8 of 8 (100%) nephrogenic adenomas, and by 17 of 17 (100%) lymphomas. Weak focal staining was noted in 5 of 12 (42%) cases of parathyroid hyperplasia/adenoma and in 6 of 17 (35%) well-differentiated neuroendocrine tumors of the pancreas. PAX 8 was not seen in other neoplasms. In metastatic neoplasms, PAX 8 was expressed by 90 of 102 (88%) metastatic renal cell carcinomas, by 57 of 63 metastatic Müllerian tumors (90%), and by 6 of 6 metastatic papillary thyroid carcinomas (100%). There was also weak focal staining for 1 of 15 metastatic small cell carcinomas and for 1 of 9 metastatic well-differentiated neuroendocrine carcinomas. PAX 8 was not seen in other metastatic neoplasms. It can be successfully identified in routinely processed tissue samples, and its expression is mostly nuclear. PAX 8 expression in non-neoplastic mature tissues is limited to the organs, the embryonic development of which depends on this transcription factor. This tissue/cell-specific expression is maintained during both neoplastic transformation and metastasis. PAX 8 is a sensitive and specific marker for tumors of renal, Müllerian, or thyroid origin in both primary and metastatic sites.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Adenoma / diagnosis
  • Adenoma / metabolism
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Neoplasm Metastasis / diagnosis
  • Neoplasms / diagnosis*
  • Neoplasms / metabolism
  • Neoplasms, Germ Cell and Embryonal / metabolism
  • Neoplasms, Germ Cell and Embryonal / pathology
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / metabolism*
  • Retrospective Studies
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology


  • Biomarkers, Tumor
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors