Immunohistochemical analysis of Ki-67, p53 and Bcl-2 expression related to histological features in gastroesophageal reflux disease
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2010
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Abstract
Background/aims: The endoscopic and histologic findings of gastroesophageal reflux disease are usually indistinct. The current study was designed to define accurately the histology in gastroesophageal reflux disease and to develop a hypothesis that reflux produces immunohistochemical changes. Methods: The study was based on the examination of endoscopic esophageal biopsy specimens obtained from 20 patients with evidence of reflux with 24-hour pH-meter monitoring and from 20 control subjects without clinical or endoscopic reflux. The pathogenesis of reflux esophagitis was discussed by comparing the histopathologic changes with determined Ki-67, p53 and Bcl-2 immunoreactivity. Results: In this study, the presence of esophagitis was determined endoscopically in only 55% of the patients with gastroesophageal reflux disease, while microscopic esophagitis was detected in 60% of them. No correlation was found between presence of endoscopic esophagitis and microscopic esophagitis in the patients with gastroesophageal reflux disease. There was a significant difference between control cases and the patients according to histological parameters, which included basal activity (p=0.006), height of papillae (p=0.006), intraepithelial neutrophils (p=0.000), intraepithelial eosinophils (p=0.006), congestion (p=0.001), and dilated intercellular spaces (p=0.006). Immunohistochemically, there was a significant difference in the expression of p53 and Ki-67 between the three study groups (patients with/without microscopic esophagitis, controls) (p<0.05). However, there was no difference in Bcl-2 between the patients with reflux and control cases. Conclusions: In this study, we considered that microscopic esophagitis does not always accompany reflux, and the lack of reliable diagnostic histologic criteria is still a serious problem for pathologists. Immunohistochemically, an increase in cell proliferative activity and p53 protein accumulation to repair oxidative DNA damage related to reflux were observed. However, the close Bcl-2 immunoreactivity in all groups that was indicated by a weak positivity suggests that the inhibition of apoptosis may not be involved in reflux esophagitis.
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Adult , Female , Gastroesophageal Reflux , Humans , Immunohistochemistry , Ki-67 Antigen , Male , Middle Aged , Proto-Oncogene Proteins c-bcl-2 , Tumor Suppressor Protein p53 , biological marker , DNA , Ki 67 antigen , protein bcl 2 , protein p53 , adult , article , cell proliferation , clinical article , controlled study , endoscopic biopsy , esophagitis , esophagus biopsy , esophagus pH , female , gastroesophageal reflux , histopathology , human , human tissue , immunohistochemistry , male , pathogenesis , protein expression , sensitivity and specificity