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OBJECTIVEThe pathogenesis of esophageal atresia (EA) remains unknown despite a relatively high incidence of this anomaly in population affecting 1 newborn per 3000 live births. The aim of this study was to examine the relative occurrence of growth factors, their receptors, neuropeptide-containing innervation, and tissue-degradating enzymes--matrix metalloproteinases--in the proximal and distal parts of the esophagus with EA.MATERIALS AND METHODSA histopathological study was conducted on 15 patients with EA. Tissues were processed for NGFRp75, PGP 9.5, TGF-β, FGFR, VEGF, EGFR and MMP-2 by means of biotin-streptavidin immunohistochemistry.RESULTSIn the control and EA-affected distal esophageal specimens, numerous and abundant NGFR-containing structures were detected, while in the proximal part of the esophagus, a decrease in their number was observed in patients. PGP 9.5 also marked neuronal structures similarly. TGF-β was found only in occasional cells in the EA-affected esophageal specimens, while control material demonstrated moderate to numerous TGF-β-containing structures. Abundance of FGFR and only occasional appearance of VEGF-positive cells were found in both the control and EA-affected material. A moderate number of connective tissue cells in controls contained EGFR. Compared with controls, the number of MMP-2 expressing cells in the EA-affected tissues was decreased in the proximal esophagus.CONCLUSIONSA decrease in PGP 9.5-containing neuronal structures in the proximal esophagus supports insufficient innervation of this part of the organ in EA. A decrease in MMP-2 positive cells in the esophageal atresia-affected proximal esophagus indicates also a possible decrease of tissue adaptive and regenerative reactions. Low expression of TGF-β and almost the absence of EGFR in the EA-affected specimens may result in disturbances of cell growth, proliferation, and differentiation, indicating a significant role of these substances in morphopathogenesis of EA. FGFR and VEGF seem not to characterize EA pathogenesis.

medicina

Growth Factors, Their Receptors, Neuropeptide-Containing Innervation, and Matrix Metalloproteinases in the Proximal and Distal Ends of the Esophagus in Children With Esophageal Atresia