Clinical pattern, risk factors and immunohistochemical markers at Barret’s esophagus

Aim of investigation. To study clinical and morphological pattern of Barret’s esophagus to improve its diagnostics and prognosis of neoplastic transformation.

Stuff and methods. 120 patients with gastroesophageal reflux disease (GERD) have been enrolled to the study. Investigation included polypositional X-ray of esophagus and stomach, esophagogastroduodenoscopy, 24-hour рН monitoring in esophagus and the stomach, morphological and immunohistochemical investigation of esophageal mucosa biopsies. Immunohistochemical investigation consisted of assessment of grade of apoptosis, proliferation, differentiation of epithelial cells of esophagus and expression of tumor marker р53 on a background of proton pump inhibitors (PPI) therapy. Statistical analysis was carried out by software pack «SPSS 13 for Windows».

Results. Frequent (in 64% of cases) development of cylindrical metaplasia of esophageal epithelium at erosive GERD (in 46% – gastric, in 18% – intestinal) was revealed. As a rule, the intestinal metaplasia of epithelium was incomplete with development of dysplasia, mainly of low grade on its background (75%). In one case on a background of high grade dysplasia adenocarcinoma has been diagnosed. Intestinal metaplasia and dysplasia were diagnosed more often in males and males/females ratio has made 5,5:1 (at dysplasia and neoplastic transformation — 9:1). Comparative analysis of clinical pattern of Barret’s esophagus and erosive esophagitis has not revealed significant differences of basic symptoms (intensity and frequency of heartburn, odynophagia, regurgitation). For Barret’s esophagus long (mean 5–14,5 years; р=0,008) and frequently relapsing course of GERD (r=0,4; р=0,01) was typical. Prevalence of smoking was higher (р=0,05) at intestinal metaplasia of epithelium (67%), than at gastric metaplasia (38 %) and uncomplicated reflux disease (35 %). Development of intestinal metaplasia and dysplasia in esophagus was accompanied by rise of apoptotic index and proliferation (р<0,05). At dysplasia of high degree and in adenocarcinoma specimens apoptotic index decreased, and proliferation continued to grow. р53 protein was not detected in multilayer squamous epithelium and at gastric metaplasia, it was found at some cells at intestinal metaplasia. Its expression was essentially increased at dysplasia and was maximal in adenocarcinoma (р><0,05). On background of PPI treatment decrease of proliferation in all types of epithelium of esophagus and suppression of apoptosis in multilayer squamous and gastric epithelium was observed. At intestinal epithelium apoptotic index grew, that correlated to esophageal mucosa inflammation degree. Conclusions. According to our data, prognosis of Barret’s esophagus development at the background of GERD is based on the set of factors: male gender, age over 50 years, relapses of erosive esophagitis several times per year, past history of GERD for more than 5 years, smoking. Increase of proliferative activity, р53 expression and decrease of apoptotic index can serve as markers of high risk of neoplastic transformation on a background of dysplasia of Barret’s esophagus epithelium.><0,05). At dysplasia of high degree and in adenocarcinoma specimens apoptotic index decreased, and proliferation continued to grow. р53 protein was not detected in multilayer squamous epithelium and at gastric metaplasia, it was found at some cells at intestinal metaplasia. Its expression was essentially increased at dysplasia and was maximal in adenocarcinoma (р<0,05). On background of PPI treatment decrease of proliferation in all types of epithelium of esophagus and suppression of apoptosis in multilayer squamous and gastric epithelium was observed. At intestinal epithelium apoptotic index grew, that correlated to esophageal mucosa inflammation degree.

Conclusions. According to our data, prognosis of Barret’s esophagus development at the background of GERD is based on the set of factors: male gender, age over 50 years, relapses of erosive esophagitis several times per year, past history of GERD for more than 5 years, smoking. Increase of proliferative activity, р53 expression and decrease of apoptotic index can serve as markers of high risk of neoplastic transformation on a background of dysplasia of Barret’s esophagus epithelium.

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