A Subpopulation Of Airway Epithelial Cells That Express Hepatocyte Nuclear Factor 4 Alpha - Its Implication In The Development Of Non-Terminal Respiratory Unit-Type Lung Adenocarcinoma

A normal counterpart and precancerous lesion that non-terminal respiratory unit (TRU) lung adenocarcinomas (LADCs) develop from have not been clarified. Non-TRU LADCs specifically express hepatocyte nuclear factor 4 alpha (HNF4 alpha). Thus, we have been interested in airway epithelial cells that express HNF4 alpha as the potential precursor of non-TRU LADC. The purposes of the present study are to report the frequency and distribution of HNF4 alpha-expressing cells at the different airway levels, and to investigate the potential significance of the expression of HNF4 alpha in the histogenesis of non-TRU LADC with a special reference to the relationship to bronchiolar metaplasia in idiopathic interstitial pneumonia. We herein identified a minor subpopulation of epithelial cells that express HNF4 alpha in a physiological state. This subpopulation was mainly located in the terminal bronchioles and had the appearance of ciliated cells, which were mutually exclusive from Clara cells and others that strongly expressed thyroid transcription factor 1. Furthermore, the expression of HNF4 alpha was similar in bronchiolar metaplastic lesions and the terminal bronchioles, and some of the metaplastic lesions showed an unequivocally higher frequency and expression level of HNF4 alpha, which was comparable to non-TRU LADC. In summary, this is the first study to describe a subpopulation of ciliated cells that express HNF4 alpha as a potential normal counterpart for non-TRU LADCs and suggests that bronchiolar metaplastic lesions that strongly express HNF4 alpha are a precancerous lesion for non-TRU LADCs.