Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2015 Dec 23;65(6):907–913. doi: 10.1136/gutjnl-2015-310748

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

PMC Copyright notice

Spatial sampling of a Barrett's segment and associated oesophageal adenocarcinoma (OAC). (A) Overview of the opened resection specimen shows columnar metaplasia across the gastro-oesophageal junction (arrows) and a nodular OAC (arrowhead). The rectangular box indicates the longitudinal strip that was sampled. (B) H&E-stained cryostat section (left) of the longitudinal strip across the gastro-oesophageal junction reveals columnar metaplasia of the distal oesophagus (arrows) and an OAC at the squamocolumnar junction (arrowhead). Submucosal gland complex (asterisk) confirms the oesophageal origin. Cytochrome c oxidase (CCO) staining of this longitudinal strip (right) shows several discontinuous epithelial patches that are CCO-deficient. The OAC is also CCO-deficient. (B) and (C) images are taken at same magnification (see scalebar). The boxed area is shown in detail in (C). (C) Overview and high-power photomicrographs of one CCO-deficient epithelial patch and the associated OAC. Note the mosaic spread of the CCO-deficient clone within the background mucosa. There are no architectural or cytological features of dysplasia. OAC shows atypical, cribriform glands, which penetrate the pre-existent muscularis mucosae. (D) Deep next-generation mitochondrial DNA (mtDNA) sequencing reveals unique mtDNA mutations within the CCO-deficient epithelial patch shown in (C). Barchart shows the variant allele fractions (VAFs) of the mutations in control (stroma) sample and in material from the clonal expansion, mtDNA mutations are indicated. The 16290C>T mutation was selected for further analysis. (E) Sanger resequencing shows that spatially distinct CCO-deficient epithelial patches and the OAC carry the same 16290C>T mtDNA mutation (see also table 1). CCO-proficient epithelium does not carry this genetic lineage marker. (F) Consecutive sections of neighbouring glands showing cardia-type metaplasia and intestinal metaplasia. Top left: H&E staining shows absence of goblet cell differentiation in non-dysplastic cardia-type epithelium (marked by arrowhead), whereas the neighbouring intestinal metaplasia shows abundant goblet cells (marked by asterisk). Top right: clonal loss of CCO activity in cardia-type epithelium (marked by arrowhead). Bottom left: CDX2 staining confirms absence of intestinalisation in CCO-deficient cardia-type metaplasia. Strong nuclear labelling is seen in neighbouring intestinal metaplasia (marked by arrowhead). Bottom right: low proliferative activity as shown by Ki67 proliferation marker stain, consistent with morphological absence of dysplasia. Arrowhead points to positive nuclear labelling.