CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer

TY - JOUR

T1 - CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer

AU - Olsen, J.

AU - Eiholm, Susanne

AU - Kirkeby, L T

AU - Espersen, Maiken Lise Marcker

AU - Jess, P

AU - Gögenür, I

AU - Olsen, Jørgen

AU - Troelsen, J.T.

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background: Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion, and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk. Methods: Tumor samples were obtained from colon cancer patients. Biopsies from tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction or in formalin and paraffin embedded (FFPE) for immunohistochemical staining. CDX2 mRNA expression was evaluated by RT-qPCR. FFPE sections were stained for MLH1, MSH2, MSH6, PMS2, and CDX2. Results: A total of 191 patient samples were included in the study and analyzed by immunohistochemistry. Of these samples, 97 were further evaluated by RT-qPCR. There was no significant difference in CDX2 mRNA expression between tumor and normal tissues. CDX2 mRNA expression was significantly lower in right-sided tumors (p< 0.05), poorly differentiated tumors (p< 0.05), and MMR-deficient tumors (p< 0.05). Similarly, CDX2 protein expression was more often low or absent in right-sided tumors (p< 0.01), poorly differentiated tumors (p< 0.001), and MMR-deficient tumors (p< 0.001). Low CDX2 protein or mRNA expression was not associated with recurrence risk. Conclusion: We found that CDX2 downregulation is associated with MMR deficiency, right-sided tumors, and poor differentiation at both the mRNA and protein level. Whether CDX2 plays an active role in tumor progression in MSI/MMR-deficient tumors remains to be elucidated.

AB - Background: Homeobox genes are often deregulated in cancer and can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. CDX2 has been implicated in differentiation, proliferation, cell adhesion, and migration. In this study, we investigated CDX2 mRNA and protein expression in relation to the clinicopathological characteristics of colon cancer, including mismatch repair status and recurrence risk. Methods: Tumor samples were obtained from colon cancer patients. Biopsies from tumor tissue and normal adjacent tissue were fixed in liquid nitrogen for RNA extraction or in formalin and paraffin embedded (FFPE) for immunohistochemical staining. CDX2 mRNA expression was evaluated by RT-qPCR. FFPE sections were stained for MLH1, MSH2, MSH6, PMS2, and CDX2. Results: A total of 191 patient samples were included in the study and analyzed by immunohistochemistry. Of these samples, 97 were further evaluated by RT-qPCR. There was no significant difference in CDX2 mRNA expression between tumor and normal tissues. CDX2 mRNA expression was significantly lower in right-sided tumors (p< 0.05), poorly differentiated tumors (p< 0.05), and MMR-deficient tumors (p< 0.05). Similarly, CDX2 protein expression was more often low or absent in right-sided tumors (p< 0.01), poorly differentiated tumors (p< 0.001), and MMR-deficient tumors (p< 0.001). Low CDX2 protein or mRNA expression was not associated with recurrence risk. Conclusion: We found that CDX2 downregulation is associated with MMR deficiency, right-sided tumors, and poor differentiation at both the mRNA and protein level. Whether CDX2 plays an active role in tumor progression in MSI/MMR-deficient tumors remains to be elucidated.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Brain Neoplasms

KW - CDX2 Transcription Factor

KW - Cell Differentiation

KW - Colonic Neoplasms

KW - Colorectal Neoplasms

KW - Down-Regulation

KW - Female

KW - Genes, Tumor Suppressor

KW - Homeodomain Proteins

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplastic Syndromes, Hereditary

KW - Protein Processing, Post-Translational

KW - Proteomics

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.yexmp.2015.11.009

DO - 10.1016/j.yexmp.2015.11.009

M3 - Journal article

C2 - 26551082

SN - 0014-4800

VL - 100

SP - 59

EP - 66

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

IS - 1

ER -