Histological and immunohistochemical analysis of lung development, with particular reference to lung hypoplasia

Using immunohistochemical (IH) staining for epithelial membrane antigen (EMA), keratin, Leu-7, Ca 19-9, secretory component (SC) and surfactant protein A (SPA) on formalin-fixed, paraffin-embedded autopsy cases of stillbirth and early neonatal death, the normal profile of IH-positive cells in the airway of the developing fetal lung was clarified. IH-positive cells first appeared in the proximal region of the lung, and then in the distal region. Keratin-positive cells and EMA-positive cells were abundant at the 10th gestational week (10 GW), the earliest stage observed in this study. Cells positive for Leu-7 and Ca 19-9 appeared during the time when bronchial branches developed, and were abundant at around 16 GW, the time of completion of bronchial branching. On the other hand, SPA- and SC-positive cells appeared after the completion of bronchial branching, and were abundant around 29 GW and 34 GW, respectively. Acinous structural development was observed in terms of radial alveolar count (RAC). Cases of lung hypoplasia defined as a lung weight to body weight ratio of under 0.012 at > or = 28 GW or under 0.015 at < 28 GW showed a rather high tendency of abnormalities of cellular differentiation revealed by IH staining.