CDX2 and villin are useful markers of intestinal metaplasia in the diagnosis of Barrett esophagus

Division of Anatomical Pathology, Hunter Area Pathology Service, Newcastle, Australia.
American Journal of Clinical Pathology (Impact Factor: 3.01). 04/2008; 129(4):571-7. DOI: 10.1309/UWK3NAHV31GFHM3J
Source: PubMed

ABSTRACT The identification of intestinal metaplasia (IM) in the esophagus is necessary for the selection of patients with Barrett esophagus (BE) for surveillance. We studied 108 esophageal biopsy and resection specimens, clinically diagnosed as BE, and stained them for CDX2, villin, HepPar-1, and cytokeratin (CK) 7 to investigate sensitivity for identifying IM. H&E-stained sections showed definite goblet cells in 94 cases. CDX2 and villin were positive in all 94 cases. Of 38 cardia- and 9 fundic-type mucosa samples associated with BE, 13 (34%) and 0 (0%) displayed CDX2 positivity and 21 (55%) and 1 (11%) displayed villin positivity, respectively. HepPar-1 was positive in 54 (57%) of 94 cases with IM and negative in the associated cardia- and fundic-type mucosa. A full-thickness CK7 staining pattern was present in 90 (96%) of samples with IM and 22 (58%) and 0 (0%) of the associated cardia- and fundic-type mucosa, respectively. None of 20 control samples of morphologically normal gastric mucosa stained for CDX2 or villin. CDX2 and villin are sensitive markers for early-stage IM and can supplement the histologic identification of this premalignant condition in the esophagus.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The definition of Barrett's oesophagus lacks consensus, particularly the requirement of intestinal metaplasia for diagnosis. Scarce information exists on the prevalence and natural history of columnar-lined oesophagus without intestinal metaplasia. To evaluate the demographics and natural history of columnar-lined oesophagus without intestinal metaplasia ≥ 2 cm in length. Patients with columnar-lined oesophagus ≥ 2 cm in length and no intestinal metaplasia in biopsy specimens from two consecutive endoscopies with at least a 1-year interval were prospectively followed. A cohort of Barrett's oesophagus patients was used as a control. Columnar-lined oesophagus without intestinal metaplasia (n = 15) had a similar gender distribution, reflux symptoms prevalence and length as those of Barrett's oesophagus (n = 205). Patients were significantly younger (28.6 vs. 60 years, P < 0.0001) and accounted for 48% of patients aged <40 years in the two cohorts, but only 1% of those aged >40 years (P < 0.001). Patient distribution in both cohorts in 5 age brackets (0-19, 20-29, 30-39, 40-49, and >50 years) was significantly different, except for patients aged 40-49 years. Intestinal metaplasia was documented in 60% of the cohort after a mean follow-up of 7.1 years. Columnar-lined oesophagus without intestinal metaplasia ≥ 2 cm is infrequent in the setting of a systematic biopsy protocol, is associated with a younger age in comparison with Barrett's oesophagus, and appears to be an intermediate step between squamous and intestinal lining of the oesophagus.
    Alimentary Pharmacology & Therapeutics 06/2012; 36(3):282-9. DOI:10.1111/j.1365-2036.2012.05170.x · 4.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Cdx2 is an essential transcription factor in the differentiation and proliferation of intestinal epithelial cells. However, the expression and role of Cdx2 in the development of intestinal cystitis glandularis (CG), a metaplastic lesion induced by chronic inflammation, remained to be explored. MATERIALS AND METHODS: Real-time PCR was used to examine Cdx2, LI-cadherin and villin expression in typical and intestinal CG along with normal bladder tissue. cDNA of Cdx2 was subcloned to the retroviral vector, pLNCX2, for subsequent transfection into human bladder urothelium cells and rat bladder urothelium. Cdx2 mRNA and protein levels as well as cell morphology and proliferation were assessed following transfection using real-time PCR, phase contrast microcopy, transmission electron microscopy, and MTT assays, respectively. RESULTS: Higher mRNA levels of Cdx2, villin and LI-cadherin were detected in intestinal CG as compared to normal bladder and typical CG and only Cdx2 groups reached statistical significance (P <0.001). Retroviral overexpression of Cdx2 resulted in increased mRNA and protein expression of Cdx2 as well as villin and LI-cadherin levels and increased cell proliferation. A distinct change in cellular morphology in which the cells resembled intestinal-like cells was also observed in vitro and in vivo. CONCLUSIONS: Cdx2 may play a critical role in regulating intestinal metaplasia in CG. Further studies will assess the potential of using Cdx2 as a marker and therapeutic target for CG.
    The Journal of urology 03/2013; DOI:10.1016/j.juro.2013.03.109 · 3.75 Impact Factor
  • Source

Full-text (2 Sources)

Available from
Jan 5, 2015