β-catenin and Her2/neu expression in rectal cancer: association with histomorphological response to neoadjuvant therapy and prognosis

Background Neoadjuvant treatment strategies have been developed to improve survival of patients with advanced rectal cancer. Since mainly patients with major histopathological response benefit from this therapy, predictive and prognostic markers are needed. We examined the association of beta-catenin and Her2/neu protein expression with histopathologic response to neoadjuvant radiochemotherapy and prognosis in patients with locally advanced rectal cancer. Methods Fifty-four patients (33 male; 21 female; median age 60.4 years) with locally advanced rectal cancer were included in this study. All patients received a neoadjuvant radiochemotherapy (50.4 Gy, 5-FU) followed by surgical resection. Histomorphologic regression was evaluated by Dworak and Cologne staging system. Major response was defined by Dworak classification when resected specimens contained less than 50% vital tumor cells (n=14) and by Cologne grading system when resected specimens contained less than 10% vital tumor cells (n=15). Intratumoral beta-catenin (nuclear/membranous) and Her2/neu (cytoplasmatic/membranous) expression was determined by immunohistochemistry in pre- and post-therapeutic specimens and correlated with clinicopathologic parameters. Results A significant association was detected between pretherapeutic membranous beta-catenin levels and response: patients with a lower beta-catenin protein expression showed significantly more often a major response compared with patients having high intratumoral protein levels (p=0.011). In addition, patients with a higher Her2/neu protein expression showed a significant survival benefit compared with patients having low intratumoral protein levels (5-year survival rate: 81% vs. low 41%; p=0.023). Conclusions The pre-therapeutic beta-catenin and Her2/neu protein expression seem to be valuable predictive and prognostic markers in the multimodality treatment of advanced rectal cancer.