Immunohistochemical expression of CDX2, beta-catenin, and TP53 in inflammatory bowel disease-associated colorectal cancer.
Fiche publication
Date publication
janvier 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHENARD Marie-Pierre, Dr FREUND Jean-Noël, Pr REIMUND Jean-Marie
Tous les auteurs :
Laurent C, Svrcek M, Flejou JF, Chenard MP, Duclos B, Freund JN, Reimund JM
Lien Pubmed
Résumé
BACKGROUND: Inflammatory bowel disease (IBD) exposes patients to an increased risk of colorectal cancer (i-CRC) and differences between i-CRC and sporadic colorectal cancer (s-CRC) pathogenesis were reported. In s-CRC, studies indicate abnormalities in the tumor-suppressor gene Cdx2. This study compared CDX2, beta-catenin, and TP53 expression in i-CRC, s-CRC, noncancer IBD, and normal control colonic mucosa. METHODS: Expression was investigated by immunohistochemistry in 10 normal, 20 s-CRC, 11 noncancer colonic IBD and 30 i-CRC samples, and in four samples of Crohn's disease (CD)-associated small bowel adenocarcinoma (i-SBA). RESULTS: In normal and noncancer IBD samples, CDX2 was confined to the colonocytes nuclei. CDX2 expression was normal in 90% of i-CRC, regardless of tumor differentiation or inflammation intensity. By contrast, CDX2 expression was altered in 45% s-CRC, particularly at the front of invasion in undifferentiated tumors. beta-Catenin was restricted to cell membrane in all controls, in 91% noncancer IBD, and in 84% i-CRC samples, whereas 35% s-CRC showed cytoplasmic redistribution and exclusive nuclear staining at the front of invasion. TP53 was strongly and homogeneously expressed in i-CRC nuclei compared to normal control or s-CRC, and increases with inflammation intensity. Nested or diffuse TP53 was found in 81.8% of noncancer IBD samples with a higher proportion of TP53-expressing cells in the most inflamed samples. CDX2, beta-catenin, and TP53 expression in CD-associated SBA appears similar to that of i-CRC. Neither Cdx2 nor beta-catenin alterations are prominent features of i-CRC. CONCLUSIONS: In i-CRC and CD-associated SBA, carcinogenesis is associated early with p53 mutations and to inflammation intensity.
Référence
Inflamm Bowel Dis. 2011 Jan;17(1):232-40