title: CDX2 as a marker of intestinal EC-cells and related well-differentiated endocrine tumors.
abstract: Gastroenteropancreatic (GEP) endocrine tumors (ETs) are neoplasms showing different hormonal profiles and different clinical and prognostic features, which depend consistently on the site of origin. Histological features and general endocrine markers do not differentiate tumors in relation to their location, making it difficult to establish the site of origin of a GEP ET that has metastasized to the liver or lymph nodes. A site-specific marker would be particularly useful in the examination of small specimens where there is not sufficient material for an extensive study of the hormonal expression. CDX2 is a transcription factor that has been recently proposed as a marker of intestinal adenocarcinomas. Our aim was to evaluate the immunohistochemical expression of CDX2 in normal tissues and in 184 formalin-fixed and paraffin-embedded ETs to verify whether it could be used to identify intestinal ETs with a high degree of sensitivity and specificity. Of these cases, 154 were primary tumors (99 GEP and 55 non-GEP tumors), 101 were well-differentiated endocrine tumors, and 53 were poorly differentiated endocrine carcinomas (PDECs). Of the cases, 30 were metastases from differently located ETs. Nuclear CDX2 immunoreactivity was found in all EC-cells (serotonin-producing cells), in about 10% of G-cells (gastrin-producing cells), in about 30% of GIP-cells (gastric inhibitory peptide cells) and in a few motilin-positive cells of the normal intestinal mucosa, while other gastrointestinal endocrine cell types were CDX2 negative. All midgut EC-cell tumors, their metastases, and two of three pancreatic EC-cell ETs were diffusely and intensely CDX2 positive. The other GEP ETs, their metastases, as well as the non-GEP ETs, were all CDX2 negative, with the exception of four PDECs, five gastrinomas and one pheochromocytoma, which were only focally positive. We conclude that CDX2 may be considered a sensitive and specific marker of midgut EC-cells and EC-cell tumors, and its expression may be useful in the diagnosis of metastases from occult ETs.
authors.affiliation: Department of Pathology, Ospedale di Circolo and University of Insubria, Varese, Italy. anapat@ospedale.varese.it
authors.forename: Stefano
authors.initials: S
authors.lastname: La Rosa
authors.forename: Elena
authors.initials: E
authors.lastname: Rigoli
authors.forename: Silvia
authors.initials: S
authors.lastname: Uccella
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Chiaravalli
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071616:CDX2 Transcription Factor; D004064:Digestive System / Q000378:metabolism*; D004701:Endocrine Gland Neoplasms / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins