epidermal-growth-factor and Barrett-Esophagus

Barrett's esophagus is an acquired metaplastic change that occurs in the distal esophagus secondary to chronic gastroesophageal reflux. This premalignant condition forms the most important risk factor for developing esophageal adenocarcinoma, which is an extremely aggressive tumor with a 5-year survival rate of less than 25%. Carcinomas that arise in the setting of Barrett's esophagus are thought to develop as part of the metaplasia-dysplasia-carcinoma sequence.. To review the current knowledge on the genomic alterations involved in the development of Barrett's esophagus and its progression to dysplasia and/or cancer.. Several changes in gene structure, gene expression, and protein structure are associated with the progression of Barrett's esophagus to adenocarcinoma. Accumulation of these changes seems to be essential, rather than the exact sequence of these changes. Multiple molecular pathways are involved and interact with each other. Alterations in tumor suppressor genes, amongst which p53 and p16, are early events in the metaplasia-dysplasia-adenocarcinoma sequence, followed by loss of cell cycle checkpoints. Ongoing genomic instability leads to cumulative genetic errors and thereby the generation of multiple clones of transformed cells.. Within the multistep process of esophageal adenocarcinogenesis, to date no single molecular marker came forward able to predict who will and who will not develop cancer in the setting of Barrett's esophagus. Instead, panels of markers need to be developed in the future allowing to indicate disease progression. Identification of crucial molecular pathways involved in esophageal adenocarcinogenesis would ultimately improve therapy and facilitate development of new treatment strategies.

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; Chromosome Aberrations; Cyclin D1; DNA, Neoplasm; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Gastroesophageal Reflux; Gene Expression Regulation, Neoplastic; Humans; Metaplasia; Microsatellite Repeats; Precancerous Conditions; Receptor, ErbB-2; Tumor Suppressor Protein p53

Barrett esophagus is a premalignant condition that may progress to adenocarcinoma. The risk of developing cancer has been estimated to be approximately 1 in 250 patient-years of observation; however, there appear to be subsets of patients at much higher risk. Risk stratification has previously been determined by histological identification of dysplasia. Several new biomarkers are being tested to help clinicians better determine the risk of cancer development. Although none of these biomarkers has been proven in a prospective study to predict the onset of cancer, they have been correlated with cancer development. Most of these are factors that have been associated with cancer development in other organs. These include assessment of cell proliferation, expression of cyclooxygenase 2, growth factors and oncogenes, secretory factors, cell cycle proteins, adhesion molecules, and aneuploidy and other genetic abnormalities. In addition to their role as potential cancer biomarkers, these factors have increasingly been reported as surrogate markers to monitor the effectiveness of conservative treatments for Barrett esophagus. In this article, biological markers are reviewed for their relevance in Barrett esophagus. Although most biological markers need to be evaluated further and, for most, prospective follow-up studies are lacking, at present abnormal ploidy status, P16 and P53 gene abnormalities, or allelic losses are the most extensively documented.

Topics: Barrett Esophagus; Biomarkers; Cyclooxygenase 2; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Isoenzymes; Male; Membrane Proteins; Ornithine Decarboxylase; Precancerous Conditions; Prostaglandin-Endoperoxide Synthases; Sensitivity and Specificity; Transforming Growth Factor alpha

There has been much interest in recent years in the potential protective role of saliva in the esophagus. Variables such as salivary volume and neutralizing capacity have been studied both during basal conditions and in response to esophageal acid exposure, in healthy subjects and in patients with esophagitis. In addition to its known neutralizing capacity, saliva also contains growth factors. These polypeptides (of which epidermal growth factor has been studied most) have cytoprotective and healing properties in various segments of the gastrointestinal tract. Therefore, a deficiency in one or more of these growth factors might be a contributing factor in the development of gastroesophageal reflux disease (GERD) or its complication, such as Barrett's metaplasia. However, human studies have produced contradictory results regarding salivary growth factor deficiency in such patients. Current methods of investigation make it difficult to assess the importance of saliva in GERD. This may be due in part to the multifactorial nature of the disease and the difficulty in long-term, selective manipulation of salivary function in humans. Given the present data in the literature, it is therefore unknown if saliva plays an important role in esophageal protection.

Topics: Acids; Animals; Barrett Esophagus; Epidermal Growth Factor; Esophagitis; Esophagus; Growth Substances; Humans; Reference Values; Saliva

Oesophageal mucosa has well established protective mechanisms, which operate within pre-epithelial, epithelial and post-epithelial compartments. Since refluxed acid and pepsin always act from the luminal side of the mucosa, protective factors like EGF, operating as a part of pre-epithelial defence, are thought to be pivotal in the maintenance of the integrity of the oesophageal mucosa. The significant contribution of salivary EGF to the quality of the oesophageal mucosal barrier has been demonstrated in an experimental setting and in a clinical scenario. Patients with low salivary EGF levels are predisposed to severe oesophageal damage if they develop gastro-oesophageal reflux and are a high-risk group for development of Barrett's oesophagus. Not only the salivary glands but also the human oesophagus has a profound ability to elaborate and release EGF. Some changes in luminal release of EGF during oesophageal mucosal exposure to intraluminal damaging factors imply its role in the oesophageal protective mechanisms. To exert biological effects within the oesophageal mucosal compartment, EGF requires binding to the ligand-binding domain of its receptor. This process results in receptor dimerisation, autophosphorylation and activation of intracellular signal transduction pathways. EGF receptors are localised on the basolateral and luminal aspect of the mucosal cells playing an important role in fast regeneration of oesophageal epithelium through the high mitotic activity of its proliferative zone. An increase in the rate of salivary EGF secretion during masticatory stimulation suggests its potential therapeutic benefit in the treatment of patients with damaged oesophageal mucosa.

Topics: Barrett Esophagus; Epidermal Growth Factor; Esophagus; Gastroesophageal Reflux; Humans; Mucous Membrane; Saliva

Topics: Adenocarcinoma; Barrett Esophagus; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Growth Substances; Humans; Transforming Growth Factor alpha; Transforming Growth Factor beta

Gastroesophageal reflux disease (GERD) may present as nonerosive reflux disease (NERD), erosive esophagitis (EE), or be complicated by Barrett's esophagus (BE). The explanation as to what determines the phenotype of GERD is awaited. Therefore, we assessed the correlation between the growth factors expression and endoscopic as histologic findings in GERD patients.. The squamous esophageal epithelium of 50 patients (20-NERD, 7-EE, 15-BE, 8 controls) was examined by: (1) magnification endoscopy with evaluation of minimal GERD changes such as: microerosions, white spots, palisade blood vessels visibility, and intrapapillary capillary loops (IPCLs) appearance, (2) histology, (3) immunohistochemistry with evaluation of the expression of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and their receptors (VEGFR and EGFR).. The expression of VEGF, but not VEGFR, EGF, and EGFR, was significantly increased in EE patients compared to NERD patients and controls. VEGF levels correlated significantly with the presence of white spots, but not with other minimal endoscopic and histologic features. The EGFR expression correlated positively with basal cell hyperplasia and enlarged IPCLs.. Our findings suggest a correlation between growth factors expression and findings in conventional endoscopy, formation of endoscopic minimal changes, and histologic lesions.

Topics: Barrett Esophagus; Carcinoma, Squamous Cell; Endoscopy, Gastrointestinal; Epidermal Growth Factor; ErbB Receptors; Esophageal Mucosa; Gastroesophageal Reflux; Humans; Phenotype; Vascular Endothelial Growth Factor A

In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett's esophagus. Using whole transcriptome profiling we found that in the presence of normal epithelial cells, dysplastic cells but not normal cells, exhibit marked down-regulation of a number of key signaling pathways, including the transforming growth factor beta (TGFβ) and epithelial growth factor (EGF). Functional assays revealed both cell types showed repressed proliferation and significant changes in motility (speed, displacement and directionality) as a result of interactions between the two cell types. Cellular interactions appear to be mediated through both direct cell-cell contact and secreted ligands. The findings of this study are important in that they reveal, for the first time, the effects of cellular communication on gene expression and cellular function between premalignant (dysplastic) epithelial cells and their normal counterparts.

Topics: Barrett Esophagus; Cell Communication; Cell Line; Cell Line, Tumor; Coculture Techniques; Culture Media, Conditioned; Disease Progression; Epidermal Growth Factor; Epithelium; Gene Expression Regulation; Humans; Sequence Analysis, RNA; Transcription, Genetic; Transcriptome; Transforming Growth Factor beta

Gastroesophageal reflux disease (GERD) is a pathology with a wide range of clinical and endoscopic manifestations. Epidermal growth factor receptor (EGFR), found in the epithelium of the digestive tract, plays an important role in epithelial repair and shows increased expression in different neoplasms, including esophageal tumors.. The purpose of this study was to evaluate EGFR expression using immunohistochemistry in esophageal biopsies obtained from patients with GERD, Barrett's esophagus, and adenocarcinoma of the esophagus.. EGFR expression was immunohistochemically determined in biopsies from 194 patients with symptoms suggestive of GERD or adenocarcinoma of the esophagus, seen at two Brazilian university hospitals between January 2003 and December 2008. Based on histopathological analysis, patients were divided into three groups: GERD, Barrett's esophagus and adenocarcinoma of the esophagus. EGFR expression was considered positive when staining was detected in the membrane.. Mean age was 55.25 years (range 30-90). Patients with GERD (n = 127) accounted for 65.5% of the sample, compared with 12.4% (n = 24) of patients with Barrett's esophagus and 22.2% (n = 43) of patients with esophageal adenocarcinoma. Immunohistochemical analysis was positive for EGFR in 19.1% of the patients (37/194), divided as follows: 8.7% (11/127) in the GERD group, 25% (6/24) in the Barrett's esophagus group, and 46.5% (20/43) in the esophageal adenocarcinoma group. Statistical analysis revealed significant differences between the three groups (p = 0.0001).. GERD patients showed lower levels of EGFR expression than patients with Barrett's esophagus or patients with adenocarcinoma of the esophagus, suggesting a direct relationship between EGFR expression and disease progression.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Epidermal Growth Factor; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Gene Expression Regulation; Humans; Male; Middle Aged

Reflux esophagitis (RO) and Barrett's esophagus (BO) can cause esophageal adenocarcinoma (OAC). The esophageal mucosa in the RO-BO-OAC cascade is chronically exposed to gastro-esophageal reflux. Epidermal growth factor (EGF) has an important role in the protection and repair of mucosal damage, and non-physiologic levels are associated with gastrointestinal tumors. The aim is to determine the functional effect of EGF gene polymorphisms on RO, BO and OAC development. A cohort of 871 unrelated Dutch Caucasians consisted of 198 healthy controls, 298 RO patients, 246 BO patients and 129 OAC patients. The frequency of the EGF-production-associated 5'UTR A+61G polymorphism was determined in these four groups. EGF immunohistochemistry was performed on BO biopsies. EGF expression was significantly lower in the G/G genotype compared with the A/G (P=0.008) and A/A (P=0.002) group. The G/G genotype was significantly more prevalent in RO (odds ratios (OR)=2.6; 95% confidence intervals (95% CI): 1.3-5.2), BO (OR=3.0; 95% CI: 1.5-6.2) and OAC (OR=4.1; 95% CI: 1.8-9.7) than in controls. The G allele is associated with reduced EGF expression and increased risk for RO, BO and OAC development. This indicates that reduced mucosal protection resulting from genetically decreased EGF expression enhances esophageal tumor development.

Topics: Adenocarcinoma; Barrett Esophagus; Cohort Studies; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Esophagitis, Peptic; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Logistic Models; Male; Middle Aged; Polymorphism, Single Nucleotide; Sex Characteristics

The assessment of cancer risk in patients with Barrett's esophagus (BE) is currently fraught with difficulty. The current gold standard method of assessing cancer risk is histological assessment, with the appearance of high-grade dysplasia (HGD) as the key event monitored. Sampling error during endoscopy limits the usefulness of this approach, and there has been much recent interest in supplementing histological assessment with molecular markers, which may aid in patient stratification.. No molecular marker has been yet validated to accurately correlate with esophageal histological progression. Here, we assessed the suitability of several membranous proteins as biomarkers by correlating their abundance with histological progression. In all, 107 patient samples, from 100 patients, were arranged on a tissue microarray (TMA) and represented the various stages of histological progression in BE. This TMA was probed with antibodies for eight receptor proteins (mostly membranous).. Epidermal growth factor receptor (EGFR) staining was found to be the most promising biomarker identified with clear increases in staining accompanying histological progression. Further, immunohistochemistry was performed using the full-tissue sections from BE, HGD, and adenocarcinoma tissues, which confirmed the stepwise increase in EGFR abundance. Using a robust H-score analysis, EGFR abundance was shown to increase 13-fold in the adenocarcinoma tissues compared to the BE tissues. EGFR was "overexpressed" in 35% of HGD specimens and 80% of adenocarcinoma specimens when using the H-score of the BE patients (plus 3 s.d.) as the threshold to define overexpression. EGFR staining was also noted to be higher in BE tissues adjacent to HGD/adenocarcinoma. Western blotting, although showing more EGFR protein in the adenocarcinomas compared to the BE tissue, was highly variable. EGFR overexpression was accompanied by aneuploidy (gain) of chromosome 7, plus amplification of the EGFR locus. Finally, the bile acid deoxycholic acid (DCA) (at neutral and acidic pH) and acid alone was capable of upregulating EGFR mRNA in vitro, and in the case of neutral pH DCA, this was NF-κB dependent.. EGFR is overexpressed during the histological progression in BE tissues and hence may be useful as a biomarker of histological progression. Furthermore, as EGFR is a membranous protein expressed on the luminal surface of the esophageal mucosa, it may also be a useful target for biopsy guidance during endoscopy.

Topics: Adenocarcinoma; Aged; Barrett Esophagus; Biomarkers, Tumor; Biopsy, Needle; Blotting, Western; Cell Transformation, Neoplastic; Cohort Studies; Disease Progression; Epidermal Growth Factor; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Middle Aged; Neoplasm Staging; Polymerase Chain Reaction; Precancerous Conditions; Predictive Value of Tests; Prognosis; RNA, Messenger; Up-Regulation

The evolutionary dynamics between interacting heterogeneous cell types are fundamental properties of neoplastic progression but can be difficult to measure and quantify. Cancers are heterogeneous mixtures of mutant clones but the direct effect of interactions between these clones is rarely documented. The implicit goal of most preventive interventions is to bias competition in favor of normal cells over neoplastic cells. However, this is rarely explicitly tested. Here we have developed a cell culture competition model to allow for direct observation of the effect of chemopreventive or therapeutic agents on two interacting cell types. We have examined competition between normal and Barrett's esophagus cell lines, in the hopes of identifying a system that could screen for potential chemopreventive agents.. One fluorescently-labeled normal squamous esophageal cell line (EPC2-hTERT) was grown in competition with one of four Barrett's esophagus cell lines (CP-A, CP-B, CP-C, CP-D) under varying conditions and the outcome of competition measured over 14 days by flow cytometry.. We demonstrate that ascorbic acid (vitamin C) can help squamous cells outcompete Barrett's cells in this system. We are also able to show that ascorbic acid's boost to the relative fitness of squamous cells was increased in most cases by mimicking the pH conditions of gastrointestinal reflux in the lower esophagus.. This model is able to integrate differential fitness effects on various cell types, allowing us to simultaneously capture effects on interacting cell types without having to perform separate experiments. This model system may be used to screen for new classes of cancer prevention agents designed to modulate the competition between normal and neoplastic cells.

Topics: Apoptosis; Ascorbic Acid; Barrett Esophagus; Cell Line, Transformed; Cell Proliferation; Coculture Techniques; Epidermal Growth Factor; Epithelial Cells; Esophagus; Humans

The epidermal growth factor (EGF) pathway is important in esophageal adenocarcinoma (EAC) tumorigenesis. We hypothesized that the EGF A61G homozygous variant genotype (GG) is (a) both a risk and poor prognostic factor for EAC and (b) associated with higher EGF serum levels in individuals with gastroesophageal reflux disease (GERD).. Using unconditional logistic regression, we compared EGF A61G in 312 EAC cases and 447 GERD-free controls, adjusting for age, gender, smoking history, and healthy adult body mass index. Using the method of Kaplan and Meier, log-rank tests, and Cox proportional hazard models, we correlated EGF A61G with overall and failure-free survival in the EAC cases. Serum EGF levels and EGF genotype (G/G versus others) were correlated in 144 GERD patients using Wilcoxon rank sum tests.. The EGF A61G G/G genotype conferred increased EAC risk, with an adjusted odds ratio of 1.81 (95% confidence interval, 1.2-2.7), and was even higher in the subgroup of EAC patients with concurrent Barrett's esophagus (adjusted odds ratio, 2.18; 95% confidence interval, 1.3-3.7). However, EGF A61G was not associated with a more aggressive phenotype or prognosis in EAC patients. Higher serum EGF levels were found in GERD patients carrying G/G compared with A/A or A/G (P = 0.03, Wilcoxon rank sum test).. The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The G/G allele was also associated with higher EGF levels in tumor-free patients with GERD. EGF genotyping can potentially identify high-risk patients with GERD and Barrett's metaplasia who might benefit from increased surveillance.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Polymorphism, Single Nucleotide; Precancerous Conditions; Risk Factors; Treatment Outcome

Growth factors, such as epidermal growth factor (EGF), are known to protect upper gut mucosa against irritants and to enhance healing of ulcerative lesions in animal models. A number of salivary growth factors are found in human saliva. The aim of this study was to determine if salivary growth factors and cytokines are deficient in patients with esophagitis or with Barrett's metaplasia. Fifteen healthy subjects, eight patients with esophagitis, and 13 patients with Barrett's metaplasia were included. Salivary concentration of EGF, FGF, IL-1, and IL-6 were measured during esophageal saline and hydrochloric acid perfusion and in the postprandial state. There was no statistically significant difference in the concentration of EGF or cytokines among the three study groups in each experimental condition or among the three experimental conditions in each group. FGF basic could not be detected in saliva. In conclusion, these findings do not support the hypothesis that a deficiency in salivary growth factors or cytokines plays a significant role in the development of mild to moderate reflux esophagitis or Barrett's metaplasia.

Topics: Adult; Aged; Barrett Esophagus; Epidermal Growth Factor; Esophagitis, Peptic; Female; Fibroblast Growth Factors; Humans; Interleukin-1; Interleukin-6; Male; Middle Aged; Peptide Fragments; Saliva

The conventional assessment of the premalignant potential of Barrett's oesophagus is unsatisfactory. However, it has recently been shown that abnormalities of growth-regulatory peptides and their receptors may be important in the pathogenesis of this condition. In an attempt to improve the diagnostic and prognostic criteria we have studied 21 consecutive patients with Barrett's oesophagus and 7 others with adenocarcinoma of the oesophagus. In each patient biopsy specimens were taken from the columnarlined oesophagus or the adenocarcinoma and from the gastric cardiac mucosa for routine histologic evaluation. Immediately adjacent specimens were taken from both the Barrett's mucosa or adenocarcinoma and from the gastric mucosa for flow-cytometric study. The latter samples were disaggregated and labelled with antibodies to epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). The flow cytometer selected cells labelled with each antibody and expressed them as a percentage of the total number of disaggregated cells (average, 5500 cells). Epidermal growth factor receptors were expressed in a greater number of cells from Barrett's mucosa, with the intestinal type or those with dysplasia, than in gastric cardiac mucosa (p less than 0.05). All seven adenocarcinoma had many more cells expressing EGF, TGF-alpha, and EGF-R than normal gastric mucosa (p less than 0.01). We conclude that flow-cytometric evaluation of EGF-R can help in the understanding of the pathogenesis of Barrett's oesophagus.

Topics: Adenocarcinoma; Adult; Aged; Autoantigens; Barrett Esophagus; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Flow Cytometry; Humans; Middle Aged; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Transforming Growth Factor alpha

Epidermal growth factor (EGF) has been implicated in mitogenesis and oncogenesis in the gastrointestinal tract. To determine the role of EGF in oesophageal disease, its quantity and distribution in the oesophageal mucosa of control subjects and patients with oesophageal disease were studied. Oesophageal biopsy specimens, taken 20-40 cm from the incisors in 72 patients, were graded histologically and adjacent specimens were taken for immunohistochemical analysis of the distribution of EGF. In patients with Barrett's columnar lined oesophagus, specimens were also taken from the gastric cardia for comparison. Twenty two biopsy specimens showed oesophagitis, 20 Barrett's mucosa, and 30 were histologically normal. EGF was found in the capillary endothelium of the normal oesophageal papillae and basal mucosa. Significantly more EGF positive papillae were found in the normal mucosa (81%) than in the inflamed mucosa (42%) (p < 0.001). The 20 patients with Barrett's mucosa showed abnormal expression of EGF in 25% of the isthmus and superficial epithelial cells. This study has shown that EGF is found only in the endothelial cells of the capillaries of the normal oesophageal mucosa and that the peptide is detectable significantly less frequently than normal in the inflamed oesophageal mucosa. EGF is also abnormally present, in large quantities, in the cytoplasm of the epithelial cells of Barrett's mucosa compared with gastric mucosa.

Topics: Adult; Aged; Aged, 80 and over; Barrett Esophagus; Cardia; Endothelium, Vascular; Epidermal Growth Factor; Epithelium; Esophageal Diseases; Esophagitis; Esophagus; Female; Gastric Mucosa; Humans; Immunohistochemistry; Male; Middle Aged; Mucous Membrane

Topics: Barrett Esophagus; Epidermal Growth Factor; Humans; Saliva; Transforming Growth Factor alpha

1. In order to assess potential abnormalities in the control of mucosal proliferation, 30 patients with Barrett's oesophagus were studied in order to evaluate the presence and distribution of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor to determine the Ki-67 labelling index in the affected oesophageal mucosa. Serial sections were analysed immunohistochemically. Ten of the patients had adenocarcinoma in the Barrett's mucosa and the other 20 had differing histological types of Barrett's mucosa (10, intestinal-type; 10, fundic- or cardiac-type). 2. The expression of transforming growth factor-alpha, epidermal growth factor and epidermal growth factor receptor was increased and the Ki-67 labelling index was higher in Barrett's mucosa compared with normal gastric mucosa. The 'intestinal-type' of Barrett's mucosa had the greatest expression of transforming growth factor-alpha, epidermal growth factor receptor and the highest Ki-67 labelling index compared with the other types of Barrett's metaplasia. Five cases of 'intestinal-type' Barrett's metaplasia had especially high Ki-67 labelling indices and these patients over-expressed both transforming growth factor-alpha and epidermal growth factor receptor. The patients with adenocarcinomas in the Barrett's mucosa also over-expressed transforming growth factor-alpha and epidermal growth factor receptor, but not epidermal growth factor, compared with normal gastric mucosa. 3. In conclusion, both normal gastric mucosa and Barrett's mucosa have potential autocrine growth regulatory mechanisms, but Barrett's mucosa has increased expression of both of the measured ligands and of the epidermal growth factor receptor.

Topics: Adenocarcinoma; Adult; Aged; Barrett Esophagus; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Female; Gastric Mucosa; Humans; Male; Middle Aged; Mucous Membrane; Transforming Growth Factor alpha

Epidermal growth factor (EGF) is implicated in the regeneration of epithelial cells at the site of inflammation or ulceration in the gastrointestinal tract. Single parotid EGF concentration and production was studied in 64 patients with Barrett's columnar lined oesophagus (CLO), in 22 patients with severe reflux oesophagitis without columnar metaplasia and in 51 normal controls. In control patients, mean salivary EGF concentration was 2790 pg/ml (median 1450 pg/ml; range 450-16,500 pg/ml) and mean single parotid EGF production was 2550 pg/min (median 1750 pg/min; range 790-18,000 pg/min). Patients with severe reflux oesophagitis had a similar EGF concentration (mean 3112 pg/ml; median 1500 pg/ml; range 300-16,000 pg/ml) and production (mean 3100 pg/min; median 2200 pg/min; range 790-17,950 pg/min) to controls. Patients with CLO had a 62 per cent lower mean EGF concentration (mean 1197 pg/ml; median 640 pg/ml; range 233-4500 pg/ml) (P less than 0.001, Mann-Whitney U test) and a 60 per cent lower EGF production (mean 1254 pg/min; median 800 pg/min; range 170-3125 pg/min) (P less than 0.001, Mann-Whitney U test) than patients with severe reflux oesophagitis. A subpopulation with malignant change in CLO (n = 16) had a similar EGF concentration and production to the CLO group as a whole (mean 1240 and 1300 pg/min, respectively). Low salivary EGF levels are associated with Barrett's CLO but not with severe oesophagitis without columnar metaplasia. EGF levels do not identify those patients who will subsequently develop malignant change.

Topics: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Barrett Esophagus; Epidermal Growth Factor; Esophageal Neoplasms; Esophagitis, Peptic; Female; Humans; Male; Middle Aged; Molecular Sequence Data; Parotid Gland; Risk Factors; Saliva