Decreased β-catenin Protein in Lungs From Human Congenital Diaphragmatic Hernia Archival Pathology Specimens: A Case-control Study

Lung hypoplasia contributes to congenital diaphragmatic hernia (CDH) associated morbidity and mortality. Changes in lung wingless-type MMTV integration site family member (Wnt)-signalling and its downstream effector beta-catenin (CTNNB1), which acts as a transcription coactivator, exist in animal CDH models but are not well characterized in humans. We aim to identify changes to Wnt-signalling gene expression in human CDH lungs and hypothesize that pathway expression will be lower than controls. We identified 51 CDH cases and 10 non-CDH controls with archival formalin-fixed paraffin-embedded (FFPE) autopsy lung tissue from 2012 to 2022. 11 liveborn CDH cases and an additional two anterior diaphragmatic hernias were excluded from the study, leaving 38 CDH cases. Messenger ribonucleic acid (mRNA) expression of Wnt-signalling effectors WNT2B and CTNNB1 was determined for 19 CDH cases and 9 controls. A subset of CDH cases and controls lung sections were immunostained for β-catenin. Clinical variables were obtained from autopsy reports. Median gestational age was 21 weeks. 81% (n = 31) of hernias were left-sided. 47% (n = 18) were posterolateral. Liver position was up in 81% (n = 31) of cases. Defect size was Type C or D in 58% (n = 22) of cases based on autopsy photos, and indeterminable in 42% (n = 16) of cases. WNT2B and CTNNB1 mRNA expression did not differ between CDH and non-CDH lungs. CDH lungs had fewer interstitial cells expressing β-catenin protein than non-CDH lungs (13.2% vs 42.4%; p = 0.006). There appear to be differences in the abundance and/or localization of β-catenin proteins between CDH and non-CDH lungs. Level III. Case-Control Study. •Animal models of congenital diaphragmatic hernia suggest that Wnt/β-catenin signalling is dysregulated in developing lungs. Whether this occurs in humans is unclear.•Using archival pathology specimens we show that β-catenin protein may be lower in interstitial lung cells from congenital diaphragmatic hernia cases when compared to controls.