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Open Access Research article

Preoperative chemoradiotherapy in rectal cancer induces changes in the expression of nuclear β-catenin: prognostic significance

Jaime Gomez-Millan1*, Lydia Perez2, Ines Aroca3, Maria del Mar Delgado4, Vanessa De Luque5, Alicia Román1, Esperanza Torres5, Soraya Ramos4, Sofia Perez6, Eloisa Bayo4 and Jose Antonio Medina1

Author Affiliations

1 Department of Radiation Oncology, University Hospital Virgen de la Victoria, Campus Teatinos s/n, Málaga, 29010, Spain

2 Department of Pathology, University Hospital Virgen de la Victoria, Malaga, Spain

3 Centro de Investigaciones Biomedicas, Granada, Spain

4 Department of Radiation Oncology, Hospital Juan Ramon Jimenez, Huelva, Spain

5 Department of Medical Oncology, University Hospital Virgen de la Victoria, Malaga, Spain

6 Department of Pathology, Hospital Juan Ramon Jimenez, Huelva, Spain

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BMC Cancer 2014, 14:192  doi:10.1186/1471-2407-14-192

Published: 15 March 2014

Abstract

Background

Preoperative chemoradiotherapy (CRT) is the cornerstone of treatment for locally advanced rectal cancer (LARC). Although high local control is achieved, overall rates of distant control remain suboptimal. Colorectal carcinogenesis is associated with critical alterations of the Wnt/β-catenin pathway involved in proliferation and survival. The aim of this study was to assess whether CRT induces changes in the expression of β-catenin/E-cadherin, and to determine whether these changes are associated with survival.

Methods

The Immunohistochemical expression of nuclear β-catenin and membranous E-cadherin was prospectively analysed in tumour blocks from 98 stage II/III rectal cancer patients treated with preoperative CRT. Tumour samples were collected before and after CRT treatment. All patients were treated with pelvic RT (46–50 Gy in 2 Gy fractions) and 5-fluorouracil (5FU) intravenous infusion (225 mg/m2) or capecitabine (825 mg/m2) during RT treatment, followed by total mesorectal excision (TME). Disease-free survival (DFS) was analysed using the Kaplan-Meier method and a multivariate Cox regression model was employed for the Multivariate analysis.

Results

CRT induced significant changes in the expression of nuclear β-catenin (49% of patients presented an increased expression after CRT, 17% a decreased expression and 34% no changes; p = 0.001). After a median follow-up of 25 months, patients that overexpressed nuclear β-catenin after CRT showed poor survival compared with patients that experienced a decrease in nuclear β-catenin expression (3-year DFS 92% vs. 43%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.02). In the multivariate analysis for DFS, increased nuclear β-catenin expression after CRT almost reached the cut-off for significance (p = 0.06).

Conclusions

In our study, preoperative CRT for LARC induced significant changes in nuclear β-catenin expression, which had a major impact on survival. Finding a way to decrease CRT resistance would significantly improve LARC patient survival.

Keywords:
Locally advanced rectal cancer; Radiotherapy; Chemotherapy; β-catenin