CDX2 as a marker for intestinal differentiation: Its utility and limitations

Abstract

CDX2 is a nuclear homeobox transcription factor that belongs to the caudal-related family of CDX homeobox genes. The gene encoding CDX2 is a nonclustered hexapeptide located on chromosome 13q12-13. Homeobox genes play an essential role in the control of normal embryonic development. CDX2 is crucial for axial patterning of the alimentary tract during embryonic development and is involved in the processes of intestinal cell proliferation, differentiation, adhesion, and apoptosis. It is considered specific for enterocytes and has been used for the diagnosis of primary and metastatic colorectal adenocarcinoma. CDX2 expression has been reported to be organ specific and is normally expressed throughout embryonic and postnatal life within the nuclei of epithelial cells of the alimentary tract from the proximal duodenum to the distal rectum. In this review, the authors elaborate on the diagnostic utility of CDX2 in gastrointestinal tumors and other neoplasms with intestinal differentiation. Limitations with its use as the sole predictor of a gastrointestinal origin of metastatic carcinomas are also discussed.

Keywords: Aberrant expression; CDX2; Colorectal carcinoma.

Figure 1

CDX2 expression. A: CDX2 expression in metastatic ileal carcinoid to the liver. Please note the presence of moderate nuclear staining; B: CDX2 expression is also seen in appendiceal goblet carcinoid (Immunohistochemistry × 400); C: CDX2 expression in cytology specimens of metastatic colonic carcinoma to the lung, supporting their colorectal origin. (Immunohistochemistry × 250); D: CDX2 expression is seen in the majority of endocervical adenocarcinomas of intestinal type (Immunohistochemistry × 400); E: CDX2 expression in endometrioid carcinoma (Immunohistochemistry × 400); F: CDX2 expression in sinonasal adenocarcinoma of intestinal type (Immunohistochemistry × 400).