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Title: Preoperative chemoradiotherapy in rectal cancer induces changes in the expression of nuclear β-catenin: prognostic significance.
Authors: Gómez-Millán, Jaime
Pérez, Lydia
Aroca, Inés
Delgado, Maria del Mar
Luque, Vanessa de
Román, Alicia
Torres, Esperanza
Ramos, Soraya
Pérez, Sofia
Bayo, Eloísa
Medina, José Antonio
metadata.dc.contributor.authoraffiliation: [Gómez-Millán, J; Román, A; Medina, JA] Department of Radiation Oncology, University Hospital Virgen de la Victoria, Málaga, Spain. [Pérez, L] Department of Pathology, University Hospital Virgen de la Victoria, Málaga, Spain. [Aroca, I] Centro de Investigaciones Biomédicas, Granada, Spain. [Delgado, MM; Ramos, S; Bayo, E] Department of Radiation Oncology, Hospital Juan Ramón Jiménez, Huelva, Spain. [Luque, V de; Torres, E] Department of Medical Oncology, University Hospital Virgen de la Victoria, Málaga, Spain. [Pérez, S] Department of Pathology, Hospital Juan Ramón Jiménez, Huelva, Spain.
Keywords: Locally advanced rectal cancer;Radiotherapy;Chemotherapy;β-catenin;Recurrencia Local de Neoplasia;Neoplasias del Recto;Quimioradioterapia;Cuidados Preoperatorios
metadata.dc.subject.mesh: Medical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Rectal Neoplasms
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Chemoradiotherapy
Medical Subject Headings::Health Care::Health Care Facilities, Manpower, and Services::Health Services::Patient Care::Preoperative Care
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Issue Date: 15-Mar-2014
Publisher: BioMed Central
Citation: Gomez-Millan J, Perez L, Aroca I, Delgado MM, Luque V De, Román A, et al. Preoperative chemoradiotherapy in rectal cancer induces changes in the expression of nuclear β-catenin: prognostic significance. BMC Cancer. 2014; 14(1):192
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.
Description: Journal Article;
metadata.dc.identifier.doi: 10.1186/1471-2407-14-192
Appears in Collections:SAS - Hospital Universitario Juan Ramón Jiménez
SAS - Hospital Universitario Virgen de la Victoria

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