CDX-2 is a nuclear transcription marker that regulates differentiation and proliferation of intestinal epithelial cells, and also serves as tumor suppressor gene.  CDX-2 is normally expressed in small and large intestine epithelium.  It is a sensitive marker for colorectal adenocarcinomas (especially with strong diffuse expression).  It can also mark non-colorectal GI adenocarcinomas, columnar cell variant of papillary thyroid carcinoma (and other variants of papillary thyroid carcinoma, classic and modular variant),  ovarian mutinous carcinomas, bladder adenocarcinomas, goblet cells in Barrett’s esophagus, along with other tumors (data in tables below). Practically speaking, if a particular tumor can have any type of intestinal differentiation, then it most likely can have CDX-2 expression.

It is important to note that antibody sensitivity can have significant inter laboratory variation due to both clone selection and antibody optimization (Borrisholt, et. al.).  Each laboratory should have a good understanding of the performance characteristics of their CDX-2 clone and optimization.

 

IHC Survey of Primary and Metastatic Caricnomas (Werling, R. W., et. al.)

 

Common expression patterns in carcinoma (Dennis, J. L, et. al.)

 

(Enriquez, M.L., et. al.)

 

CDX-2 and Villin expression in human tumors (2-3+ expression) (Werling, R.W., et. al.)

Werling, R. W., Yaziji, H., Bacchi, C. E., & Gown, A. M. (2003). CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. The American Journal of Surgical Pathology, 27(3), 303–310.  Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=American+Journal+of+Surgical+Pathology%2C+27(3)%2C+303%E2%80%93310. 

 

Dennis, J. L., Hvidsten, T. R., Wit, E. C., Komorowski, J., Bell, A. K., Downie, I., et al. (2005). Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(10), 3766–3772. doi:10.1158/1078-0432.CCR-04-2236  Link:  http://www.ncbi.nlm.nih.gov/pubmed/?term=Markers+of+adenocarcinoma+characteristic+of+the+site+of+origin%3A+development+of+a+diagnostic+algorithm 

 

Enriquez, M. L., Baloch, Z. W., Montone, K. T., Zhang, P. J., & LiVolsi, V. A. (2012). CDX2 expression in columnar cell variant of papillary thyroid carcinoma. American Journal of Clinical Pathology, 137(5), 722–726. doi:10.1309/AJCPXE3PUBWVZCGZ Link:  http://www.ncbi.nlm.nih.gov/pubmed/22523209

 

Cameselle-Teijeiro, J., Alberte-Lista, L., Peteiro-Gonzalez, D., Abdulkader-Nallib, I., Reyes-Santias, R., Soares, P., et al. (2012). CDX2 Expression in Some Variants of Papillary Thyroid Carcinoma. American Journal of Clinical Pathology, 138(6), 907–910. doi:10.1309/AJCP1BGCA6MFCNKH  Link:  http://www.ncbi.nlm.nih.gov/pubmed/23161723 

 

Borrisholt, M., Nielsen, S., & Vyberg, M. (2013). Demonstration of CDX2 is highly antibody dependant. Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 21(1), 64–72. doi:10.1097/PAI.0b013e318257f8aa Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Demonstration+of+CDX2+is+highly+antibody+dependant 

 

Werling, R. W., Yaziji, H., Bacchi, C. E., & Gown, A. M. (2003). CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. The American Journal of Surgical Pathology, 27(3), 303–310. Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=CDX2%2C+a+highly+sensitive+and+specific+marker+of+adenocarcinomas+of+intestinal+origin%3A+an+immunohistochemical+survey+of+476+primary+and+metastatic+carcinomas