CDX2 Loss With Microsatellite Stable Phenotype Predicts Poor Clinical Outcome in Stage II Colorectal Carcinoma

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Slik , K , Turkki , R , Carpen , O , Kurki , S , Korkeila , E , Sundström , J & Pellinen , T 2019 , ' CDX2 Loss With Microsatellite Stable Phenotype Predicts Poor Clinical Outcome in Stage II Colorectal Carcinoma ' , American Journal of Surgical Pathology , vol. 43 , no. 11 , pp. 1473-1482 . https://doi.org/10.1097/PAS.0000000000001356

Title: CDX2 Loss With Microsatellite Stable Phenotype Predicts Poor Clinical Outcome in Stage II Colorectal Carcinoma
Author: Slik, Khadija; Turkki, Riku; Carpen, Olli; Kurki, Samu; Korkeila, Eija; Sundström, Jari; Pellinen, Teijo
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, HUSLAB
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2019-11
Language: eng
Number of pages: 10
Belongs to series: American Journal of Surgical Pathology
ISSN: 0147-5185
URI: http://hdl.handle.net/10138/307158
Abstract: Current risk factors in stage II colorectal carcinoma are insufficient to guide treatment decisions. Loss of CDX2 has been shown to associate with poor clinical outcome and predict benefit for adjuvant chemotherapy in stage II and III colorectal carcinoma. The prognostic relevance of CDX2 in stage II disease has not been sufficiently validated, especially in relation to clinical risk factors, such as microsatellite instability (MSI) status, BRAF mutation status, and tumor budding. In this study, we evaluated the protein expression of CDX2 in tumor center and front areas in a tissue microarrays material of stage II colorectal carcinoma patients (n=232). CDX2 expression showed a partial or total loss in respective areas in 8.6% and 10.9% of patient cases. Patients with loss of CDX2 had shorter disease-specific survival when scored independently either in tumor center or tumor front areas (log rank P=0.012; P=0.012). Loss of CDX2 predicted survival independently of other stage II risk factors, such as MSI status and BRAF mutation status, pT class, and tumor budding (hazard ratio=5.96, 95% confidence interval=1.55-22.95; hazard ratio=3.70, 95% confidence interval=1.30-10.56). Importantly, CDX2 loss predicted inferior survival only in patients with microsatellite stable, but not with MSI-high phenotype. Interestingly, CDX2 loss associated with low E-cadherin expression, tight junction disruption, and high expression of ezrin protein. The work demonstrates that loss of CDX2 is an independent risk factor of poor disease-specific survival in stage II colorectal carcinoma. Furthermore, the study suggests that CDX2 loss is linked with epithelial-to-mesenchymal transition independently of tumor budding.
Subject: CDX2
stage II colorectal cancer
microsatellite instability
tumor budding
epithelial-to-mesenchymal transition
EPITHELIAL-MESENCHYMAL TRANSITION
ISLAND METHYLATOR PHENOTYPE
HOMEOBOX GENE-EXPRESSION
PROGNOSTIC VALUE
COLON-CANCER
EZRIN
ADENOCARCINOMA
MARKER
BRAF
RECOMMENDATIONS
3111 Biomedicine
3126 Surgery, anesthesiology, intensive care, radiology
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