CDX2 Immunohistochemistry
CDX2 Immunohistochemistry
CDX2 is a homeobox transcription factor involved in intestinal epithelial development and differentiation. In diagnostic IHC, it is used as a sensitive and relatively specific marker of intestinal differentiation, most commonly applied to identify adenocarcinomas of gastrointestinal origin — particularly colorectal adenocarcinoma. Staining is nuclear.
Utility and limitations
CDX2 positivity is seen in the great majority of colorectal adenocarcinomas, making it a workhorse marker when confirming intestinal-type differentiation in a metastatic adenocarcinoma of unknown primary. However, it is not colorectal-specific: CDX2 is also expressed in a range of other tumours with intestinal or intestinal-type differentiation, including gastric adenocarcinoma (particularly intestinal-type), a subset of pancreaticobiliary adenocarcinomas, mucinous ovarian tumours, and some urothelial carcinomas with glandular/intestinal metaplasia.
Loss of CDX2 expression has also been reported as a marker of aggressive behaviour and worse prognosis in a subset of colorectal cancers, and can occur in poorly differentiated or dedifferentiated tumours — so a negative result doesn’t exclude colorectal origin, especially in high-grade lesions.
Panel context
Because of these overlaps, CDX2 is best used as part of a panel rather than as a standalone site-of-origin marker:
- CK7/CK20: classic colorectal profile is CK20+/CK7−, though this pattern has well-known exceptions.
- SATB2: increasingly regarded as more specific for colorectal origin than CDX2, since SATB2 is less frequently positive in upper GI and pancreaticobiliary tumours.
- Villin: broadly supports intestinal/brush-border differentiation but shows similarly broad expression across GI sites.
Combining CDX2 with SATB2, CK7, CK20, and villin gives a more reliable picture of the site of origin than any single marker, particularly when trying to distinguish colorectal from upper GI or pancreaticobiliary adenocarcinoma in a metastatic workup.