Abstract
BackgroundCongenital Pulmonary Airway Malformation (CPAM) has an estimated prevalence between 0.87 and 1.02/10,000 live births and little is know about their pathogenesis. To improve our knowledge on these rare malformations, we analyzed the cellular origin of the two most frequent CPAM, CPAM types 1 and 2, and compared these malformations with adjacent healthy lung and human fetal lungs.MethodsWe prospectively enrolled 21 infants undergoing surgical resection for CPAM. Human fetal lung samples were collected after termination of pregnancy. Immunohistochemistry and proteomic analysis were performed on laser microdissected samples.ResultsCPAM 1 and 2 express mostly bronchial markers, such as cytokeratin 17 (Krt17) or α-smooth muscle actin (ACTA 2). CPAM 1 also expresses alveolar type II epithelial cell markers (SPC). Proteomic analysis on microlaser dissected epithelium confirmed these results and showed distinct protein profiles, CPAM 1 being more heterogeneous and displaying some similarities with fetal bronchi.ConclusionThis study provides new insights in CPAM etiology, showing clear distinction between CPAM types 1 and 2, by immunohistochemistry and proteomics. This suggests that CPAM 1 and CPAM 2 might occur at different stages of lung branching. Finally, the comparison between fetal lung structures and CPAMs shows clearly different protein profiles, thereby arguing against a developmental arrest in a localized part of the lung.
Highlights
Lung development is a complex process allowing parenchymal architecture to evolve along the bronchial organization
Congenital Pulmonary Airway Malformation (CPAM) classification was determined by the pathologist prior to IHC and proteomic analysis
The results reported in our study provide a new step in the understanding of CPAM etiology
Summary
Lung development is a complex process allowing parenchymal architecture to evolve along the bronchial organization. To establish correct bud elongation and airway branching, cellular interactions between epithelial, endothelial and mesenchymal cells are required. These interactions are dependent on the paracrine secretion of different growth factors or transcription factors. Congenital pulmonary airway malformations (CPAM) belong to a group of rare CLA whose pathological origin is still poorly understood [13]. Langston preferred the denomination “large cyst and small cyst-types”, i.e. type 1 and 2, the definition used in this paper [16] It remains as yet unclear whether or not CPAM 1 and 2 share the same origin. Congenital Pulmonary Airway Malformation (CPAM) has an estimated prevalence between 0.87 and 1.02/10,000 live births and little is know about their pathogenesis. To improve our knowledge on these rare malformations, we analyzed the cellular origin of the two most frequent CPAM, CPAM types 1 and 2, and compared these malformations with adjacent healthy lung and human fetal lungs
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