Expression of thyroid transcription factor-1 in congenital cystic adenomatoid malformation of the lung

Congenital cystic adenomatoid malformation (CCAM) is an abnormality of bran ching 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- l) 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 ty pe 1, two type 2, two type 3, and two type 4) and ii fetal lungs (3 pseudog landular, 4 canalicular, and 4 terminal sac stages) were analyzed using a r abbit poly clonal antiserum to rat TTF-1. Nuclear staining for TTF-1 was observed in ciliated and nonciliated cells o f the bronchial and bronchiolar epithelia and in cells Lining the distal ai r spaces by 12 weeks gestational age. By mid-gestation, proximal bronchial cells were TTF-1 negative, except for the basal cells, while TTF-I staining was maintained in distal bronchiolar and alveolar cells. TTF-l expression decreased in both bronchial, bronchiolar, and alveolar epithelia with advan cing gestational age and cytodifferentiation. At term, TTF-I expression per sisted in a few bronchial and bronchiolar basal cells and in all alveolar t ype II cells, whereas type I cells were negative. In CCAM, TTF-L was detected in the nuclei of epithelial cells lining the cy sts. TTF-1 was expressed in a majority of the bronchiolar-like epithelial c ells of the cysts in CCAM types 1, 2, and 3, where almost 100% of the cells were TTF-1 positive. In contrast, TTF-I expression in the alveolar-like ep ithelium 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 ab normalities in lung morphogenesis and differentiation that are distinct fro m those for CCAM type 4. The role played by TTF-l in the development of CCA M, if any, is not clear.