New insights on congenital pulmonary airways malformations revealed by proteomic analyses

• Published in: Orphanet journal of rare diseases 2019-11, Vol.14 (1), p.272-272, Article 272
• Main Authors: Barazzone-Argiroffo, C, Lascano Maillard, J, Vidal, I, Bochaton-Piallat, M L, Blaskovic, S, Donati, Y, Wildhaber, B E, Rougemont, A-L, Delacourt, C, Ruchonnet-Métrailler, I
• Format: Article
• Language: English
• Subjects: Actin; Alveoli; Births; Bronchus; Comparative analysis; Congenital defects; Congenital pulmonary airways malformation; Cysts; Cytokeratin; Development and progression; Epithelial cells; Epithelium; Etiology; Etiology (Medicine); Experiments; Fetuses; Genetic disorders; Growth factors; Immunoglobulins; Immunohistochemistry; Infants; Keratin; Lung development; Lung malformations; Lungs; Mass spectrometry; Medical research; Muscle proteins; Patients; Peptides; Pregnancy; Proteins; Proteomics; Rare diseases; Scientific imaging; Smooth muscle; Software; Surgery; Transcription factors; Ultrasonic imaging
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-019-1192-4

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. We 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. CPAM 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. This 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.