Juvenile polyps have gastric differentiation with MUC5AC expression and downregulation of CDX2 and SMAD4

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Rita Barros (Author) FMUP; Nuno Mendes (Author) FMUP; JR Howe (Author) Other; Celso Reis (Author) FMUP; C de Bolos (Author) Other; Carneiro F (Author) FMUP; David L (Author) FMUP; Raquel Almeida (Author) FMUP

Journal

Title: Histochemistry and Cell Biology

Vol. 131

Pages: 765-772

ISSN: 0948-6143

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 11 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-003-JKW

DOI: 10.1007/s00418-009-0579-z

Abstract (EN): CDX2 is a homeobox transcription factor that works as a master gene in intestinal differentiation, both in the colon and in aberrant locations such as intestinal metaplasia (IM) of the stomach. Transgenic mice with Cdx2 expression in the stomach develop IM and Cdx2(+/-) mice develop hamartomatous polyps in the colon presenting gastric differentiation. We previously observed regulation of CDX2 by the BMP/SMAD pathway in the gastric context. Here, we hypothesized that juvenile polyps, which are hamartomatous polyps caused by mutations in members of the BMP/SMAD pathway, might recapitulate the gastric differentiation observed in Cdx2(+/-) mice due to SMAD4 and CDX2 downregulation. We characterized SMAD4 and CDX2 expression in a series of 18 solitary juvenile polyps and 2 polyps from juvenile polyposis (JP) patients, one with a germline SMAD4 mutation and one with a germline BMPRIA mutation, as well as the expression of an intestinal differentiation marker, MUC2 (by immunohistochemistry and in situ hybridization), and gastric differentiation markers, MUC5AC and MUC6 (by immunohistochemistry). We observed that juvenile polyps have a heterogeneous expression of CDX2, MUC2 and SMAD4, with negative areas, and 15 of the 18 solitary polyps and the JP case with SMAD4 mutation exhibit de novo expression of MUC5AC but not MUC6. In conclusion, juvenile polyps have gastric transdifferentiation associated with downregulation of CDX2 and SMAD4, lending support to the role of the BMP/SMAD pathway in CDX2 regulation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8