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

AIM: To investigate the association between nuclear ß-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 ß-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of ß-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between ß-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 ß-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear ß-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane ß-catenin was expressed in favor of good TRG (≥ 3). Nuclear ß-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 ß-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 ß-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear ß-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity. CONCLUSION: Nuclear ß-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.