TY - JOUR
T1 - WNT-pathway activation in IBD-associated colorectal carcinogenesis
T2 - Potential biomarkers for colonic surveillance
AU - Claessen, Marian M H
AU - Schipper, Marguerite E I
AU - Oldenburg, Bas
AU - Siersema, Peter D.
AU - Offerhaus, G. Johan A
AU - Vleggaar, Frank P.
PY - 2010
Y1 - 2010
N2 - Objectives: 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 β-catenin, cyclin D1 and p53. p53 sequence analysis was performed in some cases. Results: Nuclear β-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%). Conclusion: 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 β-catenin may facilitate detection of neoplasia.
AB - Objectives: 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 β-catenin, cyclin D1 and p53. p53 sequence analysis was performed in some cases. Results: Nuclear β-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%). Conclusion: 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 β-catenin may facilitate detection of neoplasia.
KW - Colorectal cancer
KW - Inflammatory bowel disease
KW - P53
KW - Surveillance
KW - Wnt-pathway
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U2 - 10.3233/CLO-2009-0503
DO - 10.3233/CLO-2009-0503
M3 - Article
C2 - 20208143
AN - SCOPUS:77953413365
SN - 1570-5870
VL - 32
SP - 303
EP - 310
JO - Cellular Oncology
JF - Cellular Oncology
IS - 4
ER -