Expression of Thyroid Transcription Factor-1 in Congenital Cystic Adenomatoid Malformation of the Lung
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society(2014)
摘要
Congenital cystic adenomatoid malformation (CCAM) is an abnormality of branching morphogenesis of the lung. CCAM types 1, 2, and 3 exhibit a cellular composition that is different from that of CCAM type 4 when evaluated with bronchiolar and alveolar cell markers. Thyroid transcription factor 1 (TTF-1) regulates early lung development. To evaluate the potential role of TTF-1 in the development of CCAM, TTF-1 expression in CCAM was compared to that of fetal lungs at varying gestational ages. Twenty-three CCAM cases (17 type 1, two type 2, two type 3, and two type 4) and 11 fetal lungs (3 pseudoglandular, 4 canalicular, and 4 terminal sac stages) were analyzed using a rabbit polyclonal antiserum to rat TTF-1. Nuclear staining for TTF-1 was observed in ciliated and nonciliated cells of the bronchial and bronchiolar epithelia and in cells lining the distal air spaces by 12 weeks gestational age. By mid-gestation, proximal bronchial cells were TTF-1 negative, except for the basal cells, while TTF-1 staining was maintained in distal bronchiolar and alveolar cells. TTF-1 expression decreased in both bronchial, bronchiolar, and alveolar epithelia with advancing gestational age and cytodifferentiation. At term, TTF-1 expression persisted in a few bronchial and bronchiolar basal cells and in all alveolar type II cells, whereas type I cells were negative. In CCAM, TTF-1 was detected in the nuclei of epithelial cells lining the cysts. TTF-1 was expressed in a majority of the bronchiolar-like epithelial cells of the cysts in CCAM types 1, 2, and 3, where almost 100% of the cells were TTF-1 positive. In contrast, TTF-1 expression in the alveolar-like epithelium of CCAM type 4 cysts was restricted to type II cells and only 30%–60% of the lining cells were TTF-1 positive. These results support the hypothesis that CCAM types 1, 2, and 3 reflect abnormalities in lung morphogenesis and differentiation that are distinct from those for CCAM type 4. The role played by TTF-1 in the development of CCAM, if any, is not clear.
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关键词
pulmonary malformations,pulmonary epithelial cells,alveolar type ii cells,alveolar type i cells,clara cells,lung development,cell line,epithelial cell,transcription factor
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