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Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 23 December 2011, last major update November 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● Homeobox gene that encodes a nuclear transcription factor critical for intestinal embryonic development; relatively specific for intestinal epithelium (but see positive staining below)


● Also called caudal-related homeobox gene 2, caudal type homeobox transcription factor 2
● Homologue of Drosophila melanogaster homeobox gene-caudal

Uses by Pathologists

● Fairly specific marker of GI origin for adenocarcinomas, but also stains selected adenocarcinomas of other sites indicated below (Am J Surg Pathol 2003;27:303); can use to determine origin of metastatic adenocarcinoma as part of panel (Arch Pathol Lab Med 2007;131:1561)
● Distinguish primary and secondary colorectal adenocarcinomas (Arch Pathol Lab Med 2005;129:920)
● Distinguish primary bladder adenocarcinoma (CDX2-, villin-) from colorectal carcinoma extending / metastatic to bladder (CDX2+, villin+, Mod Pathol 2005;18:1217)
● Distinguish mucinous bronchioloalveolar adenocarcinoma (CDX2-) from metastatic mucinous colorectal adenocarcinoma (CDX2+, Am J Clin Pathol 2004;122:421)

Micro images

Anal gland carcinoma is CDX2- with positive internal control of normal colonic glands (fig E)

Left-bladder adenocarcinoma is CDX2+ (fig C); right-secondary colorectal carcinoma to bladder is CDX2+ vs. primary bladder tumor is weak / negative

Carcinoid tumors: primary and metastatic

Left: primary colorectal carcinomas; middle: secondary colonic tumors; right: metastasis to brain (fig 2B)

Colon: primary and secondary tumors

Left: tissue microarrays of colonic adenoma, colorectal adenocarcinomas, ovarina carcinoma; right: carcinomas of colon, duodenum and ampulla

Colonic medullary carcinoma is usually CDX2- (fig C), but colonic poorly differentiated carcinoma is usually CDX2+ (fig D)

Esophagus with Barrett esophagus: left-foveolar type dysplasia, right-adenomatous type dysplasia

Esophagus with columnar lined epithelium with and without Barrett metaplasia

Ovarian tumors (left to right): primary ovarian mucinous tumor, metastatic colorectal carcinoma, metastatic pancreatic carcinoma

Ovarian tumors (left to right): primary mucinous ovarian adenocarcinoma, primary endometrioid adenocarcinoma with squamous metaplasia, metastatic colorectal carcinoma

Stomach: epithelial dysplasia-left (fig e, e1) versus carcinoma-right

Stomach: poorly differentiated carcinoma (fig 4e)

Various (left to right): well-differentiated neuroendocrine carcinoma of pancreas, endometrial adenocarcinoma, hepatocellular carcinoma

Quality control of CDX2 staining

Positive staining - normal

● Nuclei of intestinal epithelium lining colonic villi and crypts, subset of epithelium of pancreas, stomach, esophagus
● Urachal remants of glandular type, bladder intestinal metaplasia

Positive staining - disease

Bladder: bladder/urachal adenocarcinoma, urothelial carcinoma in situ with glandular differentiation (Hum Pathol 2011;42:1653), intestinal metaplasia (83%, Mod Pathol 2006;19:1395), noninvasive urachal mucinous cystic tumor (Am J Surg Pathol 2011;35:787)
Colon: hyperplastic polyps (Am J Clin Pathol 2008;129:416), colorectal adenocarcinomas (86-100%, less if poorly differentiated)
Endometrium: lesions with squamous differentiation, especially morular-type differentiation (Hum Pathol 2008;39:1072)
Esophagus: intestinal metaplasia in Barrett esophagus (100%, Am J Clin Pathol 2008;129:571), metaplastic esophageal columnar epithelium without goblet cells (43%, Am J Surg Pathol 2009;33:1006)
Extrahepatic bile duct carcinoma: 37% (Am J Clin Pathol 2005;124:361)
Small intestinal carcinomas: 60%, usually diffuse (Am J Clin Pathol 2007;128:808), ampulla of Vater carcinomas: intestinal subtype-22%, mucinous-75% (Am J Clin Pathol 2011;135:202), intra-ampullary papillary-tubular neoplasm (Am J Surg Pathol 2010;34:1731)
Stomach: adenocarcinoma (36-70%, with variable intensity, Hum Pathol 2011;42:1777)

Carcinoid tumors: GI (varies by location, Am J Clin Pathol 2005;123:394); neuroendocrine tumors (appendix, ileum, pancreas, Am J Surg Pathol 2008;32:420)
Mucinous adenocarcinomas: lung and ovary; cervical adenocarcinoma (endometrioid > endocervical, Am J Surg Pathol 2008;32:1608); rarely other carcinomas
Signet ring cell adenocarcinoma: colon (strong, diffuse) and stomach (weak, patchy, Am J Clin Pathol 2004;121:884)
Teratoma: metastatic testicular-100% (Am J Clin Pathol 2008;130:265)

Negative staining

● Anal glands; bladder urothelium, gastric mucosa
● Carcinomas of anal gland (Arch Pathol Lab Med 2007;131:1304), breast and prostate (Am J Surg Pathol 2007;31:1323, but see Hum Pathol 2007;38:72) and urothelial carcinoma, sinonasal high grade adenocarcinoma (Am J Surg Pathol 2011;35:971)

End of Stains > CDX2

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