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

Pediatr Dev Pathol. 2000 Sep-Oct;3(5):455-61. doi: 10.1007/s100240010092.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchi / abnormalities
  • Bronchi / metabolism
  • Cystic Adenomatoid Malformation of Lung, Congenital / classification
  • Cystic Adenomatoid Malformation of Lung, Congenital / metabolism*
  • Fetal Diseases / metabolism*
  • Fetal Diseases / pathology
  • Fetus / abnormalities
  • Fetus / metabolism*
  • Gestational Age
  • Humans
  • Immunoenzyme Techniques
  • Nuclear Proteins / metabolism*
  • Pulmonary Alveoli / abnormalities
  • Pulmonary Alveoli / metabolism
  • Rabbits
  • Rats
  • Thyroid Gland / metabolism*
  • Thyroid Nuclear Factor 1
  • Transcription Factors / metabolism*


  • NKX2-1 protein, human
  • Nkx2-1 protein, rat
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors