Expression of the Intestinal Transcription Factor CDX2 in Carcinoid Tumors is a Marker of Midgut Origin

Context: Carcinoid tumors are classified according to their site of origin into foregut, midgut, or hindgut carcinoids, which have different presentations and prognosis. The intestinal transcription factor CDX2 has been found to be expressed in most intestinal adenocarcinomas but in less than one half of the gastrointestinal carcinoids according to 1 study.

Objective: To determine whether CDX2 expression in carcinoid tumors varies by the site of origin and whether CDX2 expression is retained in metastatic disease. Design.-Sections of formalin-fixed and paraffin-embedded tissue from 36 primary carcinoid tumors and 5 cases of metastatic carcinoid to the liver were immunohistochemically stained for CDX2. The percent of cells with nuclear immunoreactivity and the intensity of staining were assessed.

Results: All 18 foregut carcinoids (10 pulmonary and 8 gastric) were negative (0%) for CDX2. All 11 midgut carcinoids (100%) were positive for CDX2 with moderate to strong staining in more than 50% of the cells. Only 2 (29%) of 7 of hindgut carcinoids were CDX2-positive with the 2 positive cases showing weak to moderate staining intensity in less than 10% of the cells. Expression of CDX2 in more than 50% of tumor cells was seen only in midgut carcinoids (P < .001). CDX2 expression in metastatic tumors was consistent with the site of origin.

Conclusions: Midgut carcinoid tumors and their metastases are distinct from foregut and hindgut carcinoids in that they express high levels of CDX2. Additional studies are needed to determine whether CDX2 immunostaining may be helpful in determining the primary site of metastatic carcinoid tumors of unknown origin.