WNT-pathway activation in IBD-associated colorectal carcinogenesis: potential biomarkers for colonic surveillance.
OBJECTIVE
The Wnt-pathway dominates the sporadic carcinogenesis whereas p53 plays a pivotal role in the colitis-associated counterpart. The expression of Wnt-signaling proteins and p53 during colitis-associated carcinogenesis was determined.


METHODS
A tissue microarray was constructed with colonic samples from 5 groups of patients: controls (C, n=10), IBD without neoplasia (IBD, n=12), non-dysplastic IBD with neoplasia elsewhere in the colon (IBD-NE, n=12), dysplastic lesion in IBD (IBD-DYS, n=12), and IBD-associated colorectal cancer (IBD-CRC, n=10). Immunohistochemistry was performed for beta-catenin, cyclin D1 and p53. p53 sequence analysis was performed in some cases.


RESULTS
Nuclear beta-catenin expression was found in 0%, 0%, 50%, 55% and 100% of the patients in the C-, IBD-, IBD-NE-, IBD-DYS- and IBD-CRC-groups, respectively. Non-dysplastic IBD mucosa with neoplasia detected elsewhere showed nuclear expression in 50% of the cases compared to 0% in IBD mucosa without neoplasia (p=0.02). Cyclin D1 staining had similar expression patterns. Overexpression of p53 was only detected in the IBD-DYS (66.7%) and IBD-CRC groups (50%).


CONCLUSIONS
In contrast to previous findings, our results suggest activation of the Wnt-pathway in the early phase of colitis-associated carcinogenesis. Furthermore, as Wnt activation was observed in 50% of the IBD-NE cases, nuclear beta-catenin may facilitate detection of neoplasia.
Claessen
Marian M H
MM
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Schipper
Marguerite E I
ME
Oldenburg
Bas
B
Siersema
Peter D
PD
Offerhaus
G Johan A
GJ
Vleggaar
Frank P
FP
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D003092:Colitis; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1