Esophageal Columnar Epithelium Research Articles

СОВРЕМЕННАЯ ДИАГНОСТИЧЕСКАЯ И ЛЕЧЕБНАЯ ТАКТИКА ПРИ ПИЩЕВОДЕ БАРРЕТТА

The article represents the first experience of endoscopic mucosal cap resection of Barrett’s epithelium in Belarus. The implementation of endoscopic treatment of intestinal metaplasia into clinical practice is suggested on the basis of a case report and literature data. The comparison has been drawn between the updated clinical guidelines on the diagnosis and management of Barrett’s esophagus of different gastroenterological societies. It should be noted however that this article covers the aspect of endoscopic surveillance and treatment of esophageal columnar epithelium only. It doesn’t focus on a combination therapy that should include drug therapy of gastroesophageal reflux disease (GERD) and surgery of the lower esophageal sphincter incompetence if need be.

Barrett's esophagus network analysis revealed that arginine, alanine, aspartate, glutamate, valine, leucine and isoleucine can be biomarkers.

Identification of crucial genes and possible biomarkers which are involved in Barrett's esophagus (BE) disease was aim of this study. BE is diagnosed by endoscopy and biopsy and is characterized by esophageal columnar metaplastic epithelium. BE can convert into dysplasia that finally results cancer condition. Gene expression profiles of BE and normal gastric cardia which are characterized by GSE34619 and GPL6244 platform (1) were retrieved from gene expression omnibus (GEO). The significant differentially expressed genes (DEGs) were analyzed via protein-protein interaction network (PPI) analysis. The nodes of network were enriched via gene ontology (GO) to find biological terms. Action map of network elements was provided. Among 250 top DEGs, 100 ones were included in PPI network and KIT, CFTR, IMPDH2, MYB, FLT1, ATP4A, and CPS1 were recognized as prominent genes related to BE. Seven amino acids including arginine, alanine, aspartate, glutamate, valine, leucine and isoleucine which are related to BE were highlighted. In conclusion five central DEGs; KIT, CFTR, IMPDH2, MYB, and FLT1 were proposed as possible biomarkers for BE. However, validation and more experimental information is require to finalize the findings.

Oesophagus: A new candidate for the progenitor cell of Barrett metaplasia.

At the squamocolumnar junction of mice and humans,a new study has identified a unique population of transitional basal cells that express molecular markers of both oesophageal stratified squamous epithelium and gastrointestinal columnar epithelium. These transitional basal cells are an attractive candidate for the cell of origin for Barrett oesophagus.

Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma

BackgroundToll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett's esophagus, dysplasia and esophageal adenocarcinoma.MethodsTLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99).ResultsWe found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett's mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis.ConclusionsTLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma.

Sa1941 The Candidate Molecular Markers for Evaluating the Risk of Gastric Cancer After Helicobacter pylori Eradication

skin, gastrointestinal and genitourinary tracts, cardiac, smooth and skeletal muscle and immune cells (lymphocytes, mast cells and eosinophils). Dysregulation of NGF expression and signalling have been described in allergy, asthma, inflammation in the gut, chronic constipation, coronary artery disease and some cancers. In prostate cancer NGF stimulates tumour cell growth and metastasis and may drive nerve sprouting and infiltration. Inhibiting NGF by using blocking antibodies has a significant analgesic effect and is proposed to decrease metastatic cancer pain. Aim: ProNGF expression has not been previously described in tumours of the gastrointestinal tract. Materials and Methods: The expression of proNGF was examined by immunocytochemistry of esophageal squamous cancer (SCC) (15 cases), gastric adenocarcinoma (10 cases) and colorectal adenocarcinoma (12 cases) and corresponding normal adjacent tissues in the gut in tumour microarrays (Figure 1). Sections were scored for site of cytoplasmic staining in esophagus and cancer grade. Results: All gut epithelial tissue expressed pro-NGF. In normal oesophageal squamous epithelium expression site was diffuse, superficial or basal (Figure 2), in squamous carcinoma, staining was intense and diffuse. In adenocarcinomas (stomach and colon) staining was diffuse, and in intestinal metaplasia (IM) in the stomach, staining was more intense compared to adjacent gastric epithelium. There was no significant difference in intensity of staining by grade of cancer. Conclusions: There is significant expression of pro-NGF in squamous oesophageal and gastrointestinal columnar epithelium in both normal tissue and cancer. Pro-NGF may be therefore be a target of interest in biomarker exploration and therapeutic development for inhibition of cancer growth and cancer pain.

What the gastroenterologist needs to know about the histology of Barrettʼs esophagus

The purpose of this review is to provide clinicians with an up-to-date summary of the terminology, classification, biological characteristics, and limitations of pathology regarding Barrett's esophagus and associated neoplastic precursor lesions in order to optimize decision making when evaluating patients with this disorder. This review summarizes some of the advancements and controversies regarding the definition and diagnostic criteria for Barrett's esophagus, difficulties that arise when trying to differentiate esophageal versus gastric epithelium in gastroesophageal junction (GEJ) biopsies, the histology and biology of nondysplastic Barrett's esophagus including columnar metaplasia without goblet cells, and the limitations and diagnostic variability in interpretation of conventional and nonconventional types of dysplasia in Barrett's esophagus. The definition of Barrett's esophagus is controversial, particularly with regard to the need to identify goblet cells in esophageal biopsies. In most cases, morphologic evaluation of GEJ biopsies cannot help distinguish whether the columnar epithelium comes from the distal esophagus versus the proximal stomach. Metaplastic esophageal columnar epithelium that does not contain goblet cells nevertheless is biologically intestinalized, shows molecular abnormalities, and has been shown to be at risk for progression to cancer, but the magnitude of that risk is unknown. Interobserver agreement on the presence, grade, and type of dysplasia remains moderate at best, particularly in light of the recent recognition of nonconventional types of dysplasia, such as foveolar, serrated, and early crypt dysplasia, which make interpretation difficult. Close cooperation between clinicians and pathologists is essential in order to ensure proper interpretation of biopsy results and to provide optimal surveillance and treatment decisions.

American Gastroenterological Association Technical Review on the Management of Barrett's Esophagus

American Gastroenterological Association Technical Review on the Management of Barrett's Esophagus

Intestinal Differentiation in Metaplastic, Nongoblet Columnar Epithelium in the Esophagus

Barrett esophagus (BE) is defined by the presence of metaplastic esophageal columnar epithelium with goblet cells within endoscopically recognizable areas of the esophagus. However, some carcinomas in BE, or from the gastroesophageal junction region, develop within mucosa devoid of goblet cells. However, the biologic properties, pathogenesis, and risk of malignancy of metaplastic, esophageal nongoblet columnar epithelium, is, essentially, unknown. In this study, 89 patients with metaplastic esophageal columnar epithelium were evaluated immunohistochemically for markers of intestinal differentiation, such as MUC2, DAS-1, Villin, and CDX2, a marker of gastric differentiation (MUC5AC), and Ki67, a marker of cell proliferation. Of the 89 patients, 59 had columnar metaplasia with goblet cells (BE), which were further separated into low-density goblet cell and high-density goblet cell groups based on the percentage of crypts with goblet cells, and 30 patients had columnar metaplasia of the esophagus without goblet cells. As controls, gastric biopsies from 19 age and sex matched patients without esophageal or gastric pathology were used. The rate of positivity of the markers and the location of Ki67 staining was evaluated only in non-goblet columnar epithelium from all patient groups. Patients with metaplastic esophageal columnar epithelium without goblet cells showed positivity for MUC5AC, MUC2, DAS-1, Villin, and CDX2 in 100%, 0%, 30%, 17%, and 43% of cases, respectively. 17% of cases showed aberrant surface Ki67 positivity. These values were significantly higher than gastric controls, which showed absence of staining for all markers except MUC5AC (100%). In patients with metaplastic esophageal columnar epithelium with goblet cells (BE) a significant increased rate of staining was observed for all markers, except MUC5AC. In addition, both MUC2 and surface Ki67 staining were significantly increased in BE patients with high-density goblet cells versus those with low-density goblet cells. In a separate analysis in which metaplastic esophageal nongoblet epithelium was evaluated in areas of mucosa devoid of goblet cells compared with areas of mucosa with goblet cells, from patients who had goblet cells elsewhere in the mucosa (N=59), no significant differences were observed with regard to the percentage of cases that stained with any of the markers in the nongoblet epithelium in areas devoid of goblet cells, similar to the patient group with metaplastic esophageal epithelium without goblet cells (N=30). Similar to above, in all cases, expression of intestinal markers increased in areas of mucosa adjacent to goblet cells. This study provides evidence that metaplastic esophageal columnar epithelium without goblet cells shows phenotypic evidence of intestinal differentiation and supports the theory that squamous epithelium converts initially to nongoblet columnar epithelium before goblet cell metaplasia. Further prospective studies are needed to evaluate the pathogenetic sequence, natural history, and risk of malignancy of metaplastic esophageal nongoblet epithelium.

Metaplastic Esophageal Columnar Epithelium Without Goblet Cells Shows DNA Content Abnormalities Similar to Goblet Cell–Containing Epithelium

The mucosa of patients with columnar-lined esophagus recognized on endoscopy usually shows epithelium with and without goblet cells. Columnar epithelium with goblet cells ("Barrett's esophagus") is generally believed to represent a premalignant lesion and has been shown to contain DNA abnormalities. However, the biological properties of non-goblet columnar epithelium remain unknown. The purpose of this study was to determine the DNA content properties of non-goblet epithelium in patients with metaplastic columnar epithelium of the esophagus. Mucosal biopsies of the esophagus from 68 patients with columnar metaplasia of the esophagus (22 without goblet cells and 46 with goblet cells) and 19 patients with normal gastric mucosa (controls) were histologically evaluated for the density of goblet cells. The latter group was divided into low-density, high-density, and very high-density goblet cell subgroups. Tissue sections of non-goblet epithelium and goblet cell epithelium (where present) were evaluated by image cytometry, and high-fidelity DNA histograms were created to indicate the G0/G1 peak DNA index (DI), DNA content heterogeneity index (HI), and the percentage of cells with DNA exceeding 5N (5N-EC). G0/G1 peaks with DI>1.1 were considered aneuploid. Normal gastric controls showed a mean peak DI of 1.02+/-0.03 and an HI of 11.6+/-0.7. None of the controls revealed aneuploidy or 5N-EC. Patients with metaplastic columnar epithelium with goblet cells showed a DI of 1.15+/-0.12, HI of 18.2+/-2.1, mild aneuploidy in 54% of the cases, and 5N-EC in 15% of the cases, all of which were significantly higher than in controls. Patients with metaplastic columnar epithelium without goblet cells showed DNA content results statistically similar to those of patients with metaplastic columnar epithelium with goblet cells, and also revealed significantly higher values compared with those of controls. Furthermore, there were no significant differences in any of the key DNA content abnormalities between non-goblet and goblet cell-containing epithelium in patients with metaplastic columnar epithelium with goblet cells, or between these two types of epithelium according to the density of goblet cells. DNA content abnormalities occur with equal frequency and extent in metaplastic columnar epithelium of the esophagus without goblet cells compared with metaplastic columnar epithelium with goblet cells. These findings suggest that metaplastic non-goblet columnar epithelium of the esophagus may have neoplastic potential.

Microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasiaadenocarcinoma sequence

To investigate the microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence. Forty-one specimens were obtained from esophageal cancer (EC) patients. Histopathological assessment identified 23 squamous cell carcinomas (SCC) and 18 adenocarcinomas (ADC), including only 8 ADC with Barrett esophageal columnar epithelium (metaplasia) and dysplasia adjacent to ADC. Paraffin-embedded normal squamous epithelium, Barrett esophageal columnar epithelium (metaplasia), dysplasia and esophageal tumor tissues were dissected from the surrounding tissues under microscopic guidance. DNA was extracted using proteinase K digestion buffer, and DNA was diluted at 1:100, 1:1000, 1:5000, 1:10000 and 1:50000, respectively. Seven microsatellite markers (D2S123, D3S1616, D3S1300, D5S346, D17S787, D18S58 and BATRII loci) were used in this study. Un-dilution and dilution polymerase chain reactions (PCR) were performed, and microsatellite analysis was carried out. No statistically significant difference was found in microsatellite instability (MSI) and loss of heterozygosity (LOH) of un-diluted DNA between SCC and ADC. The levels of MSI and LOH were high in the metaplasia-dysplasia-adenocarcinoma sequence of diluted DNA. The more the diluted DNA was, the higher the rates of MSI and LOH were at the above 7 loci, especially at D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci. The sequence of metaplasia-dysplasia-adenocarcinoma is associated with microsatellite alterations, including MSI and LOH. The MSI and LOH may be the early genetic events during esophageal carcinogenesis, and genetic alterations at the D3S1616, D5S346 and D3S123 loci may play a role in the progress of microsatellite alterations.

Role of reflux oesophagitis and acid in the development of columnar epithelium in the rat oesophagus.

The role of reflux oesophagitis and acid in the development of oesophageal columnar epithelium was investigated in the rat. Twenty-four animals underwent total gastrectomy and oesophagojejunostomy, inducing reflux of duodenal contents into the oesophagus, and were divided into two groups: an 'acid' group, which drank syrup water with hydrochloric acid (pH 1.8), and a 'non-acid' group, which drank only syrup water (pH 6.5). Four rats were killed at 4, 8 and 12 weeks after surgery. Reflux oesophagitis was found in the lower portion of the oesophagus in all cases. Columnar epithelium was observed in the oesophagus of one rat in the non-acid group at week 8 and of three in the acid group at week 12. These results indicate that the development of columnar epithelium of the oesophagus is preceded by reflux oesophagitis and that acidic conditions may promote this change. Columnar epithelialization may result from metaplasia of squamous epithelium as well as from upward extension of columnar epithelium.

Controversies of the cardiac mucosa and Barrett's oesophagus

Confusion regarding the diagnosis of Barrett's oesophagus exists because of a false dogma that cardiac mucosa is normally present in the gastro-oesophageal junctional region. Recent data indicate that the only normal epithelia in the oesophagus and proximal stomach are squamous epithelium and gastric oxyntic mucosa. When this fact is recognized, it becomes easy to develop precise histological definitions for the normal state (presence of only squamous and oxyntic mucosa), metaplastic oesophageal columnar epithelium (cardiac mucosa with and without intestinal metaplasia, and oxynto-cardiac mucosa), the gastro-oesophageal junction (the proximal limit of gastric oxyntic mucosa), the oesophagus (that part of the foregut lined by squamous and metaplastic columnar epithelium), reflux disease (the presence of metaplastic columnar epithelium), and Barrett's oesophagus (cardiac mucosa with intestinal metaplasia). It is also possible to assess accurately the severity of reflux which is directly proportional to the amount of metaplastic columnar epithelium, and the risk of adenocarcinoma which is related to the amount of dysplasia in intestinal metaplastic epithelium present within the columnar lined segment of the oesophagus. Histopathological precision cannot be matched by any other modality and can convert the confusion that exists regarding diagnosis of Barrett's oesophagus to complete lucidity in a manner that is simple, accurate, and reproducible.

Risk of adenocarcinoma in Barrett's oesophagus: population based study

Endoscopic surveillance of Barrett's oesophagus is now routine.1 Cost effectiveness depends on the risk of oesophageal adenocarcinoma.2 The magnitude of this risk is unclear because most previously published studies were...

Human model of duodenogastro-oesophageal reflux in the development of Barrett's metaplasia.

Patients with an intrathoracic oesophagogastrostomy after subtotal oesophagectomy experience profound duodenogastro-oesophageal reflux (DGOR). This study investigated the degree of mucosal injury and histopathological changes in oesophageal squamous epithelium after subtotal oesophagectomy with gastric interposition in relation to the extent of postoperative DGOR. Serial endoscopic assessment and systematic biopsy at the oesophagogastric anastomosis was undertaken in 40 patients following curative radical subtotal oesophagectomy and reconstruction with a gastric conduit subjected to a pyloroplasty. Thirty patients subsequently underwent combined 24-h ambulatory pH and bilirubin monitoring. Grade I-III oesophagitis was identified in 14 patients and oesophageal columnar epithelium in 19 patients. Biopsies from columnar regeneration revealed cardiac-type epithelium in ten patients and intestinal metaplasia in nine. Seven patients followed serially showed progression from cardiac-type epithelium to intestinal metaplasia. The incidence of Barrett's metaplasia was similar irrespective of the histological subtype of the resected tumour. Patients with oesophageal columnar epithelium had significantly higher acid (P = 0.015) and bilirubin (P = 0.011) reflux. Severe DGOR occurs following subtotal oesophagectomy and provides an environment for the acquisition of Barrett's metaplasia via a sequence of cardiac epithelium and eventual intestinal metaplasia.

Prospective evaluation of multilayered epithelium in Barrett’s esophagus

OBJECTIVE: We recently identified a distinctive type of multilayered epithelium in two patients with Barrett’s esophagus, which shows morphological characteristics of both squamous and columnar epithelium. This study was performed to prospectively evaluate the prevalence of multilayered epithelium in patients with Barrett’s esophagus. METHODS: Mucosal biopsies were obtained from the squamocolumnar junction (Z-line) of 58 patients with endoscopic evidence of esophageal columnar epithelium and from the gastroesophageal junction in 21 patients without endoscopic evidence of esophageal columnar epithelium. Specimens were evaluated for the presence of multilayered epithelium and goblet cells. RESULTS: Twenty-four of 58 (41%) of the patients with endoscopic evidence of esophageal columnar epithelium had multilayered epithelium compared with only one of 21 patients (5%) in the control group ( p = 0.005). Of the 58 patients in the study group, 43 had goblet cell metaplasia and 15 did not ( p < 0.001). Only patients with goblet cell metaplasia had multilayered epithelium. Shorter lengths of columnar epithelium were noted in the 24 patients with goblet cells and multilayered epithelium compared with the 19 patients with goblet cells and no multilayered epithelium ( p < 0.05). CONCLUSIONS: Multilayered epithelium is strongly associated with goblet cell metaplasia in patients with endoscopic evidence of esophageal columnar epithelium. These data support the hypothesis that multilayered epithelium may represent a transitional stage in the development of Barrett’s esophagus.

Prospective evaluation of multilayered epithelium in Barrett's esophagus.

We recently identified a distinctive type of multilayered epithelium in two patients with Barrett's esophagus, which shows morphological characteristics of both squamous and columnar epithelium. This study was performed to prospectively evaluate the prevalence of multilayered epithelium in patients with Barrett's esophagus. Mucosal biopsies were obtained from the squamocolumnar junction (Z-line) of 58 patients with endoscopic evidence of esophageal columnar epithelium and from the gastroesophageal junction in 21 patients without endoscopic evidence of esophageal columnar epithelium. Specimens were evaluated for the presence of multilayered epithelium and goblet cells. Twenty-four of 58 (41%) of the patients with endoscopic evidence of esophageal columnar epithelium had multilayered epithelium compared with only one of 21 patients (5%) in the control group (p = 0.005). Of the 58 patients in the study group, 43 had goblet cell metaplasia and 15 did not (p < 0.001). Only patients with goblet cell metaplasia had multilayered epithelium. Shorter lengths of columnar epithelium were noted in the 24 patients with goblet cells and multilayered epithelium compared with the 19 patients with goblet cells and no multilayered epithelium (p < 0.05). Multilayered epithelium is strongly associated with goblet cell metaplasia in patients with endoscopic evidence of esophageal columnar epithelium. These data support the hypothesis that multilayered epithelium may represent a transitional stage in the development of Barrett's esophagus.

Acid Suppression and Reepithelialization after Ablation of Barrett’s Esophagus

The role of acid reflux in the development of esophageal columnar epithelium was first described in the early 1970s in the canine esophageal reflux model. In the presence of acid reflux, columnar epithelium developed at the site of induced esophageal mucosal injury. When reflux was suppressed, most epithelium reverted back to squamous mucosa. Similar findings in human patients with Barrett’s esophagus (BE) who were treated with laser ablation were first described in 1993. While acid suppression with antireflux surgery or proton pump inhibitors (PPIs) has proven insufficient to completely reverse BE, ablation of the lesion followed by acid suppression may be a promising option. Although at least one report disputes the importance of complete acid suppression following mucosal ablation of BE, most investigators use full-dose PPI therapy following ablation, in the belief that full acid suppression provides an environment that allows the esophageal progenitor cell to develop squamous mucosa. This article provides a review of the literature to date regarding ablative therapies and acid suppression for patients with BE.

Correlation of Ultrastructural Aberrations With Dysplasia and Flow Cytometric Abnormalities in Barrett's Epithelium

Barrett's esophagus develops as a complication of chronic gastroesophageal reflux and predisposes patients to the development of dysplasia and adenocarcinoma of the esophagus. Because light microscopy of dysplasia in Barrett's esophagus shows diminished or absent mucus, we used transmission electron microscopy to compare cytoplasmic organelles required for mucus production in dysplastic and nondysplastic esophageal columnar epithelium. These observations of the rough endoplasmic reticulum, Golgi apparatus, and secretory granules were correlated with histologic interpretations and flow cytometric measurements of abnormalities of DNA content. Ultrastructural abnormalities included depletion and alteration of organelles required for mucus biosynthesis. These abnormalities often were accompanied by cells with markedly distended rough endoplasmic reticulum and massive accumulation of cytoplasmic glycogen aggregates. All 9 patients who had Barrett's dysplasia with or without early adenocarcinoma had ultrastructural abnormalities, as did 3 of 8 patients whose biopsy histology was indefinite for dysplasia. Abnormalities measured by flow cytometry correlated well with the presence of these ultrastructural aberrations. All 9 patients with Barrett's dysplasia with or without early adenocarcinoma had abnormalities observed by electron microscopy and aneuploidy or increased G2/tetraploid fractions measured by flow cytometry. Two of the 3 patients whose biopsies were indefinite for dysplasia and who had ultrastructural abnormalities also had aneuploidy or increased G2/tetraploid fractions. Neither ultrastructural nor flow cytometric abnormalities were found in the remaining 5 patients whose biopsies were indefinite for dysplasia, in 19 of 22 patients with Barrett's specialized metaplasia, or in any of the 7 patients with gastroesophageal reflux disease without Barrett's specialized metaplasia. Two of the 22 patients with Barrett's specialized metaplasia had distended rough endoplasmic reticulum in rare cells, and one other had an aneuploid cell population. We conclude that neoplastic progression in Barrett's esophagus is associated with abnormalities of cytoplasmic organelles required for mucus production. With few exceptions, these ultrastructural aberrations correspond to the presence of dysplasia or of aneuploidy or increased G2/tetraploid fractions. Electron microscopy and flow cytometery detect abnormalities associated with the development of dysplasia and cancer in Barrett's esophagus that may be biologically significant.

The relationship of endocrine cells, dysplasia and carcinoembryonic antigen in Barrett's mucosa to adenocarcinoma of the oesophagus.

This study was undertaken to assess the prevalence and characteristic hormonal profile of endocrine cells in Barrett's mucosa and to determine to what extent this profile was shared by endocrine cells of adenocarcinomas arising therefrom. In addition, lower oesophageal carcinomas, not associated with columnar metaplasia, were examined to see if they exhibited a different hormonal profile. The patients studied comprised 43 who had had multiple oesophageal biopsies. 35 who had had oesophagogastric resection for adenocarcinoma arising in Barrett's mucosa and 26 in whom the resection showed no metaplastic epithelium adjacent to tumour. Argyrophil cells were present in 90% of biopsies and resections of Barrett's mucosa combined, irrespective of the histological type of metaplastic epithelium. By immunocytochemistry the most frequently identified substance in mucosal endocrine cells was serotonin (82%) followed by somatostatin (54%), secretin (22%) and pancreatic polypeptide (17%). Gastrin, bombesin, cholecystokinin, ACTH and substance P were not identified in metaplastic mucosa in any case. The difference in expression of serotonin by endocrine cells of tumours arising in Barrett's mucosa (31%) and those not (3.8%) was statistically significant (P less than 0.0186). Carcinoembryonic antigen (CEA) was demonstrated in 60% of oesophageal carcinomas, both endocrine positive and endocrine negative. Focal CEA expression was seen in 4.6% of biopsies and 14% of Barrett's mucosa adjacent to tumour. These results indicate a higher prevalence of endocrine cells in Barrett's mucosa than hitherto documented and suggest that serotonin may be a useful marker in distinguishing between primary oesophageal and putative gastric cancers at the gastro-oesophageal junction. The identification of CEA in oesophageal columnar epithelium is of little value in predicting the development of malignancy.

Cell Proliferation in Esophageal Columnar Epithelium (Barrett’s Esophagus)

In order to correlate histopathology and cell turnover in esophageal tissue in patients with esophageal columnar epithelium, biopsy specimens from 11 patients were studied. Two of the patients had adenocarcinoma of the esophagus not present in the specimens studied. In the heterogeneous esophageal columnar epithelium, the DNA synthesis phase averaged 10.4 +/- 0.3 hr; labeling index of cells in the crypt-like structures was 23.3 +/- 0.3%; generation time was 44.6 +/- 1.2 hr, and the mitotic index was 1.82 +/- 0.07%. Significant differences were not present among specimens with columnar epithelium but they differed from cell proliferation in adjacent squamous epithelium where S phase was similar but labeling and mitotic indexes were lower and generation time increased to 105 +/- 6 hr. In the 2 patients with adenocarcinoma of the esophagus, and in 1 of 9 without adenocarcinoma, labeling of surface columnar cells after brief exposure to [3H]thymidine was present suggests that this may be a manifestation of early malignant change.