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Original Article
In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity
  1. Mohammad H Derakhshan1,
  2. Elaine V Robertson1,
  3. Yeong Yeh Lee1,2,
  4. Tim Harvey3,
  5. Rod K Ferrier3,
  6. Angela A Wirz1,
  7. Clare Orange3,
  8. Stuart A Ballantyne4,
  9. Scott L Hanvey4,
  10. James J Going3,
  11. Kenneth EL McColl1
  1. 1Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
  2. 2School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kalantan, Malaysia
  3. 3Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
  4. 4Gartnavel General Hospital, NHS Greater Glasgow & Clyde, Glasgow, UK
  1. Correspondence to Professor Kenneth E L McColl, Institute of Cardiovascular & Medical Sciences, 44 Church Street, Glasgow, G11 6NT, UK; Kenneth.McColl{at}


Introduction Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus.

Methods We used the squamocolumnar junction (SCJ), antral and body biopsies from the 52 Helicobacter pylori-negative healthy volunteers who had participated in our earlier physiological study and did not have hiatus hernia, transsphincteric acid reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia. The densities of inflammatory cells and reactive atypia were scored at squamous, cardiac and oxyntocardiac mucosa of SCJ, antrum and body. Slides were stained for caudal type homeobox 2 (CDX-2), villin, trefoil factor family 3 (TFF-3) and liver–intestine (LI)-cadherin, mucin MUC1, Muc-2 and Muc-5ac. In addition, biopsies from 15 Barrett's patients with/without IM were stained and scored as comparison. Immunohistological characteristics were correlated with parameters of obesity and high-resolution pH metry recording.

Results Cardiac mucosa had a similar intensity of inflammatory infiltrate to non-IM Barrett's and greater than any of the other upper GI mucosae. The immunostaining pattern of cardiac mucosa most closely resembled non-IM Barrett's showing only slightly weaker CDX-2 immunostaining. In distal oesophageal squamous mucosa, expression of markers of columnar differentiation (TFF-3 and LI-cadherin) was apparent and these correlated with central obesity (correlation coefficient (CC)=0.604, p=0.001 and CC=0.462, p=0.002, respectively). In addition, expression of TFF-3 in distal oesophageal squamous mucosa correlated with proximal extension of gastric acidity within the region of the lower oesophageal sphincter (CC=−0.538, p=0.001).

Conclusions These findings are consistent with expansion of cardia in healthy volunteers occurring by squamo columnar metaplasia of distal oesophagus and aggravated by central obesity. This metaplastic origin of expanded cardia may be relevant to the substantial proportion of cardia adenocarcinomas unattributable to H. pylori or transsphincteric acid reflux.


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