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. 2013 Oct 28;19(40):6876-82.
doi: 10.3748/wjg.v19.i40.6876.

Overexpression of nuclear β-catenin in rectal adenocarcinoma is associated with radioresistance

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Overexpression of nuclear β-catenin in rectal adenocarcinoma is associated with radioresistance

Lin Wang et al. World J Gastroenterol. .

Abstract

Aim: To investigate the association between nuclear β-catenin overexpression in rectal adenocarcinoma and radioresistance.

Methods: A retrospective analysis was conducted. The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent short-course preoperative radiotherapy and radical resection. The expression of β-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of β-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between β-catenin expression and clinicopathological characteristics was also analyzed. Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance.

Results: Nuclear β-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear β-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane β-catenin was expressed in favor of good TRG (≥ 3). Nuclear β-catenin expression in tumor cell differentiation (P = 0.018), lymph node metastasis (P = 0.022), and TRG (P < 0.001) showed significant differences. Univariate analyses demonstrated that radioresistance is associated with nuclear β-catenin overexpression (P < 0.001). In addition, logistic multivariate regression analysis indicated that only three factors, namely, tumor size (P < 0.001), tumor cell differentiation (P < 0.001), and nuclear β-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear β-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity.

Conclusion: Nuclear β-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.

Keywords: Colorectal cancer; Preoperative radiotherapy; Radioresistance; Rectal cancer; β-catenin.

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Figures

Figure 1
Figure 1
β-catenin expression in biopsy specimens and resected tumor tissues (× 200). A: Nuclear β-catenin was overexpressed in biopsy specimens from patients who exhibited resistance to preoperative radiotherapy; B: β-catenin presented mostly in a membrane-associated staining pattern in biopsy specimens from patients who exhibited hyper-radiosensitivity; C: Nuclear β-catenin was overexpressed in specimens with poor tumor regression grading (TRG) (≤ 2); D: β-catenin presented mostly in a membrane-associated staining pattern in specimens with good TRG (≥ 3).

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