J Martinez-Useros1, I Moreno2, M J Fernandez-Aceñero3, M Rodriguez-Remirez2, A Borrero-Palacios2, A Cebrian2, T Gomez Del Pulgar2, L Del Puerto-Nevado2, W Li2, A Puime-Otin4, N Perez4, M S Soengas5, J Garcia-Foncillas6. 1. Translational Oncology Division, OncoHealth Institute, Health Research Institute - University Hospital "Fundación Jiménez Díaz"-UAM, Av. Reyes Católicos 2, 28040, Madrid, Spain. javier.museros@oncohealth.eu. 2. Translational Oncology Division, OncoHealth Institute, Health Research Institute - University Hospital "Fundación Jiménez Díaz"-UAM, Av. Reyes Católicos 2, 28040, Madrid, Spain. 3. Department of Pathology, Clinico San Carlos University Hospital, Madrid, Spain. 4. Department of Pathology, University Hospital "Fundación Jiménez Díaz"-UAM, Madrid, Spain. 5. Melanoma Research Group, Spanish National Cancer Research Centre, Madrid, Spain. 6. Translational Oncology Division, OncoHealth Institute, Health Research Institute - University Hospital "Fundación Jiménez Díaz"-UAM, Av. Reyes Católicos 2, 28040, Madrid, Spain. jgfoncillas@gmail.com.
Abstract
BACKGROUND: Limited data are available regarding the ability of biomarkers to predict complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Complete response translates to better patient survival. DEK is a transcription factor involved not only in development and progression of different types of cancer, but is also associated with treatment response. This study aims to analyze the role of DEK in complete pathological response following chemoradiotherapy for locally advanced rectal cancer. METHODS: Pre-treated tumour samples from 74 locally advanced rectal-cancer patients who received chemoradiation therapy prior to total mesorectal excision were recruited for construction of a tissue microarray. DEK immunoreactivity from all samples was quantified by immunohistochemistry. Then, association between positive stained tumour cells and pathologic response to neoadjuvant treatment was measured to determine optimal predictive power. RESULTS: DEK expression was limited to tumour cells located in the rectum. Interestingly, high percentage of tumour cells with DEK positiveness was statistically associated with complete pathological response to neoadjuvant treatment based on radiotherapy and fluoropyrimidine-based chemotherapy and a marked trend toward significance between DEK positiveness and absence of treatment toxicity. Further analysis revealed an association between DEK and the pro-apoptotic factor P38 in the pre-treated rectal cancer biopsies. CONCLUSIONS: These data suggest DEK as a potential biomarker of complete pathological response to treatment in locally advanced rectal cancer.
BACKGROUND: Limited data are available regarding the ability of biomarkers to predict complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Complete response translates to better patient survival. DEK is a transcription factor involved not only in development and progression of different types of cancer, but is also associated with treatment response. This study aims to analyze the role of DEK in complete pathological response following chemoradiotherapy for locally advanced rectal cancer. METHODS: Pre-treated tumour samples from 74 locally advanced rectal-cancerpatients who received chemoradiation therapy prior to total mesorectal excision were recruited for construction of a tissue microarray. DEK immunoreactivity from all samples was quantified by immunohistochemistry. Then, association between positive stained tumour cells and pathologic response to neoadjuvant treatment was measured to determine optimal predictive power. RESULTS:DEK expression was limited to tumour cells located in the rectum. Interestingly, high percentage of tumour cells with DEK positiveness was statistically associated with complete pathological response to neoadjuvant treatment based on radiotherapy and fluoropyrimidine-based chemotherapy and a marked trend toward significance between DEK positiveness and absence of treatment toxicity. Further analysis revealed an association between DEK and the pro-apoptotic factor P38 in the pre-treated rectal cancer biopsies. CONCLUSIONS: These data suggest DEK as a potential biomarker of complete pathological response to treatment in locally advanced rectal cancer.
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