PAX8 is expressed in pancreatic well-differentiated neuroendocrine tumors and in extrapancreatic poorly differentiated neuroendocrine carcinomas in fine-needle aspiration biopsy specimens

Cancer Cytopathol. 2011 Jun 25;119(3):193-201. doi: 10.1002/cncy.20136. Epub 2011 Feb 15.


Background: PAX (paired box) genes encode a family of transcription factors important for organogenesis. Recently, PAX8 has been recognized as a potential immunohistochemical marker of pancreatic neuroendocrine tumors. The authors evaluated PAX8 expression in fine-needle aspiration biopsies of neuroendocrine tumors to establish whether PAX8 immunohistochemistry can be used as an ancillary marker of pancreatic origin for neuroendocrine tumors.

Methods: Fine-needle aspiration biopsies from 72 neuroendocrine tumors were evaluated for PAX8 expression: 32 primary and 23 metastatic well-differentiated neuroendocrine tumors (25 pancreatic, 13 pulmonary, 3 ileal, 2 duodenal, 1 rectal, 1 ovarian, and 10 primary site unknown) and 17 poorly differentiated neuroendocrine carcinomas (11 pulmonary, 1 pancreas, 1 breast, 1 thymus, and 3 primary site unknown).

Results: Among well-differentiated neuroendocrine tumors, only tumors from the pancreas were PAX8 positive (14 of 25, 56%) whereas no cases of pulmonary (0 of 13), ileal (0 of 3), duodenal (0 of 2), rectal (0 of 1), or ovarian (0 of 1) well-differentiated neuroendocrine tumors were positive for PAX8. One of 10 (10%) well-differentiated neuroendocrine tumors of unknown primary origin was PAX8 positive. Among poorly differentiated neuroendocrine carcinomas, PAX8 expression was identified in 1 of 1 (100%) pancreatic, 1 of 1 (100%) thymic, 4 of 11 (36%) pulmonary, and 0 of 1 (0%) breast carcinomas. One of 3 (33%) poorly differentiated neuroendocrine carcinomas of unknown primary origin was PAX8 positive.

Conclusions: Pancreatic well-differentiated neuroendocrine tumors frequently express PAX8, which can help distinguish pancreatic primary tumors from tumors of other anatomic sites. In contrast, PAX8 expression in poorly differentiated neuroendocrine carcinomas is not specific for pancreatic origin and can be seen in extrapancreatic poorly differentiated neuroendocrine carcinomas.

MeSH terms

  • Biopsy, Needle
  • Cell Differentiation
  • Humans
  • Immunohistochemistry
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology


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