The homeodomain protein CDX2 is an early marker of Barrett’s oesophagus

• Published in: Journal of clinical pathology 2004-10, Vol.57 (10), p.1063-1068
• Main Authors: Moons, L M G, Bax, D A, Kuipers, E J, van Dekken, H, Haringsma, J, van Vliet, A H M, Siersema, P D, Kusters, J G
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemistry; Aged; Aged, 80 and over; Barrett Esophagus - metabolism; Barrett Esophagus - pathology; Barrett’s oesophagus; Biological and medical sciences; Biomarkers - analysis; Biopsy; CDX2; CDX2 Transcription Factor; Endoscopy; Epithelium - chemistry; Epithelium - pathology; Esophageal Neoplasms - chemistry; Esophagus; Esophagus - chemistry; Esophagus - pathology; Female; gastro-oesophageal reflux disease; Gastroenterology. Liver. Pancreas. Abdomen; GORD; Homeodomain Proteins - analysis; Homeodomain Proteins - genetics; Humans; Immunohistochemistry - methods; Investigative techniques, diagnostic techniques (general aspects); Male; Medical prognosis; Medical sciences; Middle Aged; Morphology; Mucin-2; Mucins - analysis; Mucins - genetics; Mucous membrane; Original; Other diseases. Semiology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; PCR; Phosphatase; polymerase chain reaction; Proteins; reflux oesophagagitis; Reverse Transcriptase Polymerase Chain Reaction; reverse transcription; RNA, Messenger - analysis; SIE; Small intestine; specialised intestinal epithelium; Statistics, Nonparametric; Transcription factors
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2003.015727

Background: In Barrett’s oesophagus (BO), squamous epithelium is replaced by specialised intestinal epithelium (SIE). Transcription factors associated with intestinal differentiation, such as CDX2, may be involved in BO development. Aim: To investigate CDX2 expression in BO, squamous epithelium, and oesophageal adenocarcinoma (ADC). Methods: CDX2 expression was assessed in 245 samples—167 biopsies of the columnar lined segment and 38 squamous epithelial biopsies of 39 patients with histologically confirmed BO (10 with ADC). Forty biopsies from 20 patients with reflux oesophagitis (RO) without BO were also evaluated. CDX2 protein was investigated immunohistochemically in 138 biopsies from 16 patients with BO, four with ADC, and 20 with RO. Cdx2 and Muc2 mRNA were detected semiquantitatively using 88 BO biopsies and squamous epithelium from 19 BO patients, and when present from ADC. Results: SIE was present in 53/79 biopsies from the columnar lined segment; CDX2 protein was seen in all epithelial cells, but not in biopsies containing only gastric metaplastic epithelium (26/79), or in squamous epithelium (0/40) of patients with RO. Cdx2 mRNA was detected in all biopsies with goblet cell specific Muc2 transcription—indicative of SIE. Low Cdx2 mRNA expression was seen in 6/19 squamous epithelium samples taken 5 cm above the squamocolumnar junction of BO patients. Conclusion: CDX2 protein/mRNA is strongly associated with oesophageal SIE. Cdx2 mRNA was present in the normal appearing squamous epithelium of one third of BO patients, and may precede morphological changes seen in BO. Therefore, pathways that induce Cdx2 transcription in squamous epithelial cells may be important in BO development.