Cdx2 as a marker for neuroendocrine tumors of unknown primary sites

Lori A. Erickson, Bettina Papouchado, Haytham Dimashkieh, Shuya Zhang, Nobuki Nakamura, Ricardo V. Lloyd

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


The transcription factors CDX1 and CDX2 are homeobox genes that regulate development of the epithelium of the small and large intestine. A few studies have shown that Cdx2 protein expression is useful in the diagnosis of adenocarcinomas as well as neuroendocrine tumors of the small and large intestine. To examine the utility of Cdx2 in recognizing neuroendocrine tumors of unknown primary sites, we analyzed 224 primary and metastatic neuroendocrine tumors by immunohistochemistry. The specificity of the antibody reaction was confirmed by Western blotting. Cdx2 antibody stained all primary and most metastatic midgut carcinoid tumors. A few rectal and pulmonary carcinoids were positive, while gastric carcinoids were negative for Cdx2. One of five small cell carcinomas (20%) of the colon was positive for Cdx2, while all pulmonary small cell carcinomas were negative. Neuroendocrine tumors of the pituitary, parathyroid, medullary thyroid carcinomas, paragangliomas, pheochromocytomas and Merkel cell carcinomas were all negative for Cdx2. Western blot analysis of seven cases showed a 40 kDa band in both primary and metastatic midgut carcinoid tumors. These results indicate that Cdx2 can be very useful in recognizing metastatic neuroendocrine carcinomas of unknown primary sites, especially when they are derived from the small intestine.

Original languageEnglish (US)
Pages (from-to)247-252
Number of pages6
JournalEndocrine Pathology
Issue number3
StatePublished - Sep 2004


  • Carcinoid tumor
  • Cdx2
  • Neuroendocrine

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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