Growth factors in the proximal and distal ends of esophagus in children with esophageal atresia (ea)

The pathogenesis of EA remains unknown despite relatively high incidence of this anomaly in population. Aim of study was examination of relative distribution of growth factors, tissue degradation markers and neuropeptide-containing innervation in the proximal and distal end of esophagus. Histopathological study was conducted on 15 EA patients. Tissues were processed for NGFR p75, PGP 9.5, TGFbeta, FGFR, VEGF, EGFR and MMP-2 by use of biotin-streptavidin immunohistochemistry. In control and EA affected distal esophagus numerous and abundant NGFR-containing structures were detected with decrease of their number in proximal part of organ in patients. Also PGP 9.5 marked neuronal structures similarly. TGFbeta was found in occasional cells in EA esophagus, while controls demonstrated moderate to numerous TGFbeta-containing structures. Abundance of FGFR and occasional appearance of VEGF positive cells was found in both controls and patients. Moderate connective tissue cells in controls contained EGFR. Compared to controls, in EA tissues the number of MMP-2 expressing cells was decreased in the proximal esophagus. Using nonparametric Kruskal-Wallis Test statistical significant differences between groups were for PGP95, TGFbeta, EGFR and MMP-2. The decrease of PGP 9.5-containing neuronal structures in proximal esophagus supports insufficient innervation of this part of organ in EA. Decrease of MMP-2 positive cells in EA affected proximal esophagus indicates also the possible decrease of tissue adaptive reactions. Low expression of TGFbeta and almost absence of EGFR may deal with disturbances in cell growth, proliferation and differentiation indicating significant role of these substances in morphopathogenesis of EA