Morphogenesis of Metaplastic Changes in Gastroesophageal Reflux Disease

Scientific Essay 2012 9 Pages

Medicine - Internal Medicine



The aim of research is studying of morphogenesis of metaplastic changes in esophageal mucous and defining diagnostic and prognostic criteria in Barrett Esophagus (BE) disease.

Materials for histological and immunnohistochemical research were mucosal biopsies of distal esophagus received from 79 patients with clinical and endoscopic indicators of BE.

Immunohistochemical research with using markers CK7 and CK20 is characterized by high sensitivity, specificity and accuracy allowing defining a phenotype of various types of metaplastic processes at endoscopically defined Barrett’s Esophagus.

Moderate CK 20 expression CK20, high level of Ki67 expression and P53 in mucous epithelium of cardial type testifies about transformation of cylindrical gastric epithelium in intestinal that confirms existence of a transition form of metaplasia in intestinal and can be a precursory diagnostic symptom of Barret’s Esophagus development.

Markers Ki67 and P53 are predictors of dysplastic and malignant cell’s regeneration

due to gradual increase in its expression with the maximal values in biopsies of adenocarcinoma.

Keywords: morphology, diagnostics, esophagus.

Gastroezophageal reflux disease is an important medical and social-economic problem of the modern society [1; 2]. The relevance of studying etiopatogenetic and diagnostic aspects of GERD is defined of its abundance, clinical significance, further strong complications and difficulty of their early diagnostics [3; 4].

Special significance gastroezophageal reflux disease got in the last years. The attention of clinicisits is paid on development of heavy form of disease, Barrett’s Esophagus (BE) which is considered as before - cancer stage which can bring to adenocarcinoma of esophagus [5; 6; 9].

Despite the significant amount of publication for the last 20 years, a question about origin of cylindrical epithelium in mucous of esophagus remains debatable still. Existence of "Flame’s tongues» at endoscopic research estimates by clinical doctors as "Barrett's Esophagus", which has morphological manifestation - specialized intestinal metaplasia in mucous of esophagus. But in the majority of researches patomorphologist does not confirm this diagnosis and defines other types of gastric metaplasia.

The questions are “whether are they self-contained forms or stages of development of specialized intestinal metaplasias” and “In which metaplasia takes place the risk of development of neoplastic processes”. The main purpose of research is searching of rational treatment’s protocol and scientifically data about immunohistochemical (IGC) definition of metaplasia’s phenotype for application in the daily practice.

Research objective: searching of morphogenesis of metaplastic changes in mucous of esophagus and defining of diagnostic and prognostic criteria at Barrett's esophagus.


Material for morphological researches was biopsy of mucous (distal parts of esophagus) of 79 patients with clinical signs of BE.

Biopsy was carried out during esophagogastroduodenoscopy manipulation with using of endoscopic station Olympus Evis Exera 2, series 180, which supports modes of high optical resolution and mode of narrow spectral visualization.

Endoscopic research of struck esophagus included border definition between esophagus and stomach (Z-line). The aiming biopsy was received only from the suspicious centers in the bottom third of esophagus, located more proximally than the Z-line and separated from a stomach with the strip of normal epithelium not less than 1, 5 cm wide.

In addition to standard histological research with using of coloring (hematoksilin and eosine), we carried out immunohistochemical reactions with cytokeratins 7 and 20 (CK7 and CK 20), which allow to define phenotypic characteristics of a cylindrical epithelium and to estimate its role in development of metaplastic changes which can reveal early stages of intestinal metaplasia.

The CK 7(marker of differentiation of stomach cell’s epithelium) is in norm. The CK 20 carries to the intermediate filaments, makes structure basis of an epithelial cells [5] and also is the marker of differentiation of intestinal cells epithelium. In norm it meets in epithelium of glands in thickly intestine.

Studying of proliferate activity of epitheliocytes carried out by means of Ki67 marker, which is found in all phases of mitotic cycle, except G0.

P53 marker – protein regulator of apoptosis and cell’s cycle was used for definition of

dysplastic processes degree and forecast of development of malignant process in all groups of our research [9].

Intensity of expression for each marker was estimated with semiquantitative method: – -negative, + - weak, ++ - moderate, +++ - expressed.

Viewing and photography carried out with OLYMPUS CX-41 microscope.


The analysis of biopsies (mucous bottom third) of patients with clinic -endoscopic signs of BE showed an in homogeneity of received results.

In all cases in remained mucous of esophagus it was able to see some manifestations of chronic esophagitis corresponding to morphological criteria of reflux esophagitis and being shown by lymphocytic, histiocytic infiltration with impurity of plasmocytes in plate of mucous. Activity of inflammation was characterized by leukocytic infiltration both in stroma, and in interepithelial zone of the multilayer flat epithelium (MFE). It should be noted existence of a small amount of eosinocytes. Besides, moderately expressed signs of a circulatory disturbance in the form of plethora of vessels of different caliber, perivascular petekhial hemorrhages and stroma hypostasis were defined. Pays attention an acanthosis with lengthening of nipples MPE exceeding 60% of thickness of epithelium and basal cell's hyperplasia of exceeding 20% of thickness of epithelium. In some cases erosion and sharp ulcers are found.

A variety of metaplastic changes attracts attention. In 21% of cases of metaplasia researches of gastric type are found, it is morphologically reminding mucous the stomach, covered by the high cylindrical epithelium. Round or oval cores of epithelium cells occupy basal part of a cell; around cores cytoplasm is eosinophilic (picture. 1a and 1b).


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Title: Morphogenesis of Metaplastic Changes in Gastroesophageal Reflux Disease