Published online Oct 28, 2013. doi: 10.3748/wjg.v19.i40.6876
Revised: July 29, 2013
Accepted: September 16, 2013
Published online: October 28, 2013
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.
Core tip: In this paper we investigated the relationship between overexpression of nuclear β-catenin in rectal adenocarcinoma and radioresistance. We first confirmed that nuclear β-catenin overexpression in rectal adenocarcinoma is associated with radioresistance. Most importantly, we found that nuclear β-catenin-based prediction achieved a 83% accuracy, 65% sensitivity and 88% specificity for radioresistance. We provided a novel possible molecular mechanism to explain the radioresistance in rectal adenocarcinoma and thus may provide a new therapeutic target for enhancing radiosensitivity.