title: CDX2 downregulation is associated with poor differentiation and MMR deficiency in colon cancer.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, DK-4000, Roskilde, Denmark; Department of Surgery, Koege-Roskilde University Hospital, Køgevej 7-13, DK-4000, Roskilde, Denmark. Electronic address: josn@ruc.dk.
authors.forename: J
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Department of Pathology, Roskilde University Hospital, Køgevej 7-13, DK-4000, Roskilde, Denmark. Electronic address: seh@regionsjaelland.dk.
authors.forename: S
authors.initials: S
authors.lastname: Eiholm
authors.affiliation: Department of Surgery, Koege-Roskilde University Hospital, Køgevej 7-13, DK-4000, Roskilde, Denmark. Electronic address: lenk@regionsjaelland.dk.
authors.forename: L T
authors.initials: LT
authors.lastname: Kirkeby
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, DK-4000, Roskilde, Denmark; The Molecular Unit, Department of Pathology, Herlev University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Denmark. Electronic address: mlme@ruc.dk.
authors.forename: M L M
authors.initials: ML
authors.lastname: Espersen
authors.affiliation: Department of Surgery, Koege-Roskilde University Hospital, Køgevej 7-13, DK-4000, Roskilde, Denmark. Electronic address: pjss@regionsjaelland.dk.
authors.forename: P
authors.initials: P
authors.lastname: Jess
authors.affiliation: Department of Surgery, Koege-Roskilde University Hospital, Køgevej 7-13, DK-4000, Roskilde, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark. Electronic address: igo@regionsjaelland.dk.
authors.forename: I
authors.initials: I
authors.lastname: Gögenür
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark. Electronic address: jolsen@sund.ku.dk.
authors.forename: J
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, DK-4000, Roskilde, Denmark. Electronic address: troelsen@ruc.dk.
authors.forename: J T
authors.initials: JT
authors.lastname: Troelsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D040901:Proteomics
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins
keywords: CDX2; Cancer biomarkers; Colon cancer; Gastroenterology; Mismatch repair