Innervation, Motility Peptide, and Extracellular Matrix Remodeling Markers in Proximal and Distal Esophageal Tissue from Children with Esophageal Atresia

Background and Objectives: Esophageal atresia (EA) is associated with dysmotility and postoperative morbidity, which may reflect congenital abnormalities of innervation and extracellular matrix (ECM) remodeling. This study compared immunoreactivity for protein gene product 9.5 (PGP 9.5), motilin, three matrix metalloproteinases (MMP-1, MMP-2, and MMP-9), and three tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, and TIMP-4) among proximal EA, distal EA, and control esophageal tissues. Materials and Methods: Twenty-two formalin-fixed, paraffin-embedded EA tissue specimens (10 proximal and 12 distal segments) and five control specimens were evaluated using semiquantitative immunohistochemistry. Nonparametric methods were used for group comparisons, and associations were assessed using Spearman rank correlations. Results: Epithelial MMP-1 differed among the groups (p = 0.043) and was lower in proximal EA than in controls (pairwise p = 0.036). MMP-2 differed in the epithelium (p = 0.019) and connective tissue (p = 0.022); controls had higher values in the pairwise comparisons. Connective-tissue TIMP-2 also differed among the groups (p = 0.021) and was lower in proximal EA than in controls (pairwise p = 0.0017). PGP 9.5, MMP-9, TIMP-1, and TIMP-4 showed no significant differences in arithmetic mean values among the groups. Motilin’s immunoreactivity was more pronounced in proximal EA, but epithelial immunoreactivity did not differ significantly among the groups. Exploratory, unadjusted correlations among neural, motility-related, and ECM-remodeling markers were observed in EA tissue. Conclusions: The reported differences were specific to the segment and tissue compartment. MMP-2 was lower in distal EA epithelium and in connective tissue from both EA segments than in controls, whereas connective-tissue TIMP-2 was lower in proximal EA. Motilin did not differ significantly among the groups. The correlation findings require confirmation in analyses that adjust for multiple testing.