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ß-catenin, Cox-2 and p53 immunostaining in colorectal adenomas to predict recurrence after endoscopic polypectomy

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Abstract

Background

Endoscopic polypectomy significantly reduces the incidence of colorectal cancer, but recurrence rates are high, especially for adenomas with advanced histology. The present guidelines recommend re-colonoscopy 3 to 5 years later. Due to limited resources, more precise predictions of adenoma recurrence are required.

Design

Lesions from 109 patients with colorectal adenomas recruited into a randomized, placebo-controlled chemoprevention trial with mesalazine were included. Formalin-fixed paraffin-embedded tissue sections were stained for ß-catenin, cyclooxygenase-2 (Cox-2), and p53 and scored. Adenoma recurrence rates were recorded after 3 years and associated with clinical and immunohistochemical parameters by contingency table analysis.

Results

After 3 years, adenomas recurred in 51.4 % of patients. Out of 109 adenomas, 95 met at least one criterion of advanced adenoma (size >1 cm, villous histology, high-grade intraepithelial neoplasia). There was no influence of age, sex, size or villous histology on adenoma reappearance, whilst the number of adenomas at baseline was positively associated with recurrence (p = 0.003). In contrast, ß-catenin nuclear localisation, Cox-2 expression and p53 nuclear expression were significantly associated with adenoma recurrence after 3 years (ß-catenin: p = 0.002; Cox-2: p = 0.001; p53: p = 0.001). Combining these three markers led to a negative predictive value of 88.5 % and a sensitivity of 94.6 %. (OR = 13.54)

Conclusions

Scoring each single parameter and, more strongly, the combination of all three parameters of the expression of ß-catenin, Cox-2 and p53 in colorectal adenoma tissue may be a useful negative predictor for adenoma recurrence in patients with advanced colorectal adenomas.

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Acknowledgments

The study was supported by the PURE grant of the State of North-Rhine-Westfalia to AT and WS. We are also grateful to the Falk Foundation for supporting the GAPPS trial. We thank Dr. Frank Seidensticker for coordinating the GAPPS trial upon initiation, and we thank the biostatistician Dr. S. Lange, Witten, Germany, for supervising the statistical analysis.

Disclosures

The authors CPP, MR, DH, WS, ARS and AT have received honoraria for lectures from Falk Pharma GmbH. CPP, MR and WS have received research support from Falk Pharma GmbH.

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Correspondence to Andrea Tannapfel.

Additional information

Linda Brand and Johanna Munding contributed equally and should be considered co-first authors. Anke Reinacher-Schick and Andrea Tannapfel contributed equally and should be considered co-last authors

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Brand, L., Munding, J., Pox, C.P. et al. ß-catenin, Cox-2 and p53 immunostaining in colorectal adenomas to predict recurrence after endoscopic polypectomy. Int J Colorectal Dis 28, 1091–1098 (2013). https://doi.org/10.1007/s00384-013-1667-z

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  • DOI: https://doi.org/10.1007/s00384-013-1667-z

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