Immunohistochemical expression of CDX2, β-catenin, and TP53 in inflammatory bowel disease-associated colorectal cancer.
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, β-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. β-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, β-catenin, and TP53 expression in CD-associated SBA appears similar to that of i-CRC. Neither Cdx2 nor β-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.
Laurent
Camille
C
Département de Pathologie, Pôle de Biologie, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France. reimund-jm@chu-caen.fr
Svrcek
Magali
M
Flejou
Jean-François
JF
Chenard
Marie-Pierre
MP
Duclos
Bernard
B
Freund
Jean-Noël
JN
Reimund
Jean-Marie
JM
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000071616:CDX2 Transcription Factor; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C495270:CTNNB1 protein, human; D018398:Homeodomain Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin