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Home > A. Molecular pathology > CDX2


MIM.600297 13q12.3

Monday 15 December 2003

Definition: Cdx2 is a transcriptional regulator important in the early differentiation and maintenance of intestinal epithelium. CDX-2 is a caudal-type homeobox gene, encoding a transcription factor that plays an important role in proliferation and differentiation of intestinal epithelial cells. The utility of antibodies to CDX2 in the identification of adenocarcinomas of the gastrointestinal tract, particularly colorectal adenocarcinomas, in both primary and metastatic settings is well established.

Function - Expression

CDX2 is a caudal-related homeobox gene encoding a nuclear transcription factor that plays a key role in the development and differentiation of fetal and adult intestinal epithelial cells.

CDX2 is specifically expressed in normal epithelium of small bowel and colorectum and in the great majority of carcinomas arising in these sites.

IHC marker

- CDX2 is a marker of enteric differentiation and is positive in >90% of colorectal adenocarcinomas.

  • However, CDX2 can be positive in any carcinoma that shows enteric differentiation, and thus is not entirely colorectal-specific.
  • Interestingly, medullary carcinomas of the colorectum are frequently CK20-negative and CDX2-negative, in line with the concept of MSI.

- CDX2 expression may be seen in hepatocellular carcinomas and does not exclude the diagnosis. doi : 10.1016/j.humpath.2016.12.029


CDX2 is a highly sensitive and specific marker for differentiating colorectal carcinomas from pulmonary tumors and is also helpful for discriminating tumors of different origin along the gastrointestinal tract when used in conjunction with different mucin types.

Aberrant CDX2 expression is commonly seen in intestinal metaplasia occurring in stomach and esophagus.

Different studies reported CDX2 immunostaining also in :
- gastric carcinomas with intestinal-type differentiation,
- gastrointestinal carcinoids,
- mucinous carcinomas of the ovary and pancreas,
- in other intestinal-type adenocarcinomas occurring in different locations.

CDX2 expression decreases progressively with the advancing stage of gastric cancers, suggesting a possible tumor suppressor role (19820687).

- Yolk sac tumor

  • CDX2 can be expressed by endodermal cells (23124968) and in Yolk sac tumor (24444105, 22895825, 19578052, 22008025, 16959714).
  • The role of CDX-2 in the differentiation of intestinal/enteric epithelial cells may contribute to the formation of trophoblastic, glandular, villous, or cystic structures in germ cell tumors of the testes.
  • The expression of CDX2 in a variety of malignant germ cell tumors of the testes may be a potential pitfall in metastatic tumors of unknown primary, which are thought to be of gastrointestinal/colorectal origin but are actually from a clinically occult testicular tumor.

CDX2 fusion gene

- ETV6-CDX2 fusion gene by t(12;13)(p12;q12-14) in

  • chronic myelogenous leukemia (CML) in transformation
  • myelodysplastic syndrome (MDS)
  • acute myeloid leukemia (9920852)
  • acute non lymphocytic leukemia (ANLL)
  • B-acute lymphocytic leukemias (B-ALL)
  • T-acute lymphocytic leukemias (T-ALL)

- CDX2 is mutated in colorectal cancer.


- PDX-1, CDX-2, TTF-1, and CK7: a reliable immunohistochemical panel for pancreatic neuroendocrine neoplasms. Chan ES, Alexander J, Swanson PE, Jain D, Yeh MM. Am J Surg Pathol. 2012 May;36(5):737-43. PMID: 22498824

- Divergent Expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in Dysplasia and Intramucosal Adenocarcinomas With Intestinal and Foveolar Morphology: Is This Evidence of Distinct Gastric and Intestinal Pathways to Carcinogenesis in Barrett Esophagus? Khor TS, Alfaro EE, Ooi EM, Li Y, Srivastava A, Fujita H, Park Y, Kumarasinghe MP, Lauwers GY. Am J Surg Pathol. 2012 Mar;36(3):331-342. PMID: 22261707

- The role of cdx proteins in intestinal development and cancer. Cancer Biol Ther. Guo RJ, Suh ER, Lynch JP. 2004 Jul;3(7):593-601. PMID: 15136761

- CDX2 expression in the intestinal-type gastric epithelial neoplasia: frequency and significance. Park do Y, Srivastava A, Kim GH, Mino-Kenudson M, Deshpande V, Zukerberg LR, Song GA, Lauwers GY. Mod Pathol. 2010 Jan;23(1):54-61.
PMID: 19820687

- Comprehensive evaluation of CDX2 in invasive cervical adenocarcinomas: immunopositivity in the absence of overt colorectal morphology. Sullivan LM, Smolkin ME, Frierson HF Jr, Galgano MT. Am J Surg Pathol. 2008 Nov;32(11):1608-12. PMID: 18753946

- Aberrant Cdx2 expression in endometrial lesions with squamous differentiation: important role of Cdx2 in squamous morula formation. Wani Y, Notohara K, Saegusa M, Tsukayama C. Hum Pathol. 2008 Jul;39(7):1072-9. PMID: 18495206

- Expression of CDX2 in benign tissue and adenocarcinoma of the prostate. Herawi M, De Marzo AM, Kristiansen G, Epstein JI. Hum Pathol. 2007 Jan;38(1):72-8. PMID: 16949907

- Value of CDX2, villin, and alpha-methylacyl coenzyme A racemase immunostains in the distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma. Suh N, Yang XJ, Tretiakova MS, Humphrey PA, Wang HL. Mod Pathol. 2005 Sep;18(9):1217-22. PMID: 15803184

- Aberrant expression of CDX2 in metaplastic and inflammatory epithelium of the urinary bladder. Steininger H, Mueller H, Marquardt L. Am J Surg Pathol. 2005 Sep;29(9):1252. PMID: 16096418

- Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Chu PG, Schwarz RE, Lau SK, Yen Y, Weiss LM. Am J Surg Pathol. 2005 Mar;29(3):359-67. PMID: 15725805

- Aberrant expression of CDX2 in the metaplastic epithelium and inflammatory mucosa of the gallbladder. Osawa H, Kita H, Satoh K, Ohnishi H, Kaneko Y, Mutoh H, Tamada K, Ido K, Sugano K. Am J Surg Pathol. 2004 Sep;28(9):1253-4. PMID: 15316330

- Immunophenotypic differences between intestinal-type and low-grade papillary sinonasal adenocarcinomas: an immunohistochemical study of 22 cases utilizing CDX2 and MUC2. Cathro HP, Mills SE. Am J Surg Pathol. 2004 Aug;28(8):1026-32. PMID: 15252308

- Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Rossi G, Murer B, Cavazza A, Losi L, Natali P, Marchioni A, Migaldi M, Capitanio G, Brambilla E. Am J Surg Pathol. 2004 Apr;28(4):442-52. PMID: 15087663

- Cdx2 as a marker of epithelial intestinal differentiation in the esophagus. Phillips RW, Frierson HF Jr, Moskaluk CA. Am J Surg Pathol. 2003 Nov;27(11):1442-7. PMID: 14576477

- CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Werling RW, Yaziji H, Bacchi CE, Gown AM. Am J Surg Pathol. 2003 Mar;27(3):303-10. PMID: 12604886