A subpopulation of airway epithelial cells that express hepatocyte nuclear factor 4α - its implication in the development of non- terminal respiratory unit-type lung adenocarcinoma
Koji Okudela1, Hiromasa Arai2, Hideya Kitamura3, Tomohisa Baba3, Hideaki Mitsui1, Takehisa Suzuki1, Misaki Sugiyama4, Emi Honda4, Mai Matsumura1, Tamiko Takemura4, Toshiaki Kataoka1, Chihiro Koike1, Yoko Tateshi1, Michihiko Tajiri2, Takashi Ogura3 and Kenichi Ohashi1
1Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Divisions of 2General Thoracic Surgery, 3Respiratory Medicine, and 4Pathology, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Kanagawa, Japan
Offprint requests to: Koji Okudela, Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. e-mail: kojixok@yokohama-cu.ac.jp
Summary. 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 4α (HNF4α). Thus, we have been interested in airway epithelial cells that express HNF4α as the potential precursor of non-TRU LADC. The purposes of the present study are to report the frequency and distribution of HNF4α-expressing cells at the different airway levels, and to investigate the potential significance of the expression of HNF4α 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 HNF4α 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 HNF4α 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 HNF4α, which was comparable to non-TRU LADC. In summary, this is the first study to describe a subpopulation of ciliated cells that express HNF4α as a potential normal counterpart for non-TRU LADCs and suggests that bronchiolar metaplastic lesions that strongly express HNF4α are a precancerous lesion for non-TRU LADCs. Histol Histopathol 34, 1217-1227 (2019)
Key words: HNF4α expression, Airway epithelia, Bronchiolar metaplasia, Non-TRU lung adenocarcinoma
DOI: 10.14670/HH-18-098