Squamous cell metaplasia in the human lung: molecular characteristics of epithelial stratification

Squamous cell metaplasia (SCM) is a frequent epithelial alteration of the human tracheobronchial mucosa. This review pays particular attention to the fact that SCM can mimic esophageal, and in some instances even skin-type differentiation, showing striking similarities not only in morphology but also in terms of gene expression. Therefore, characterization of this dynamic process lends insight into the process of stratification, squamous cell formation, and "keratinization" in a pathologically relevant in vivo situation in man. First, the concept of metaplasia is presented with certain historical viewpoints on histogenesis. Then, the morphological characteristics of normal bronchial epithelium are compared with the altered phenotype of cells in SCM. These changes are described as a disturbance of the finely tuned balance of differentiation and proliferation through the action of a variety of extrinsic and intrinsic factors. Molecular aspects of altered cell/cell and cell/extracellular matrix interactions in stratified compared with single-layered epithelia are discussed with reference to SCM in the lung. Intracellular organizational and compositional changes are then summarized with special emphasis on the differential distribution of the cytokeratin (CK) polypeptides. Finally, the still unresolved problems of the histogenetic relationships between normal bronchial mucosa, SCM, and pulmonary neoplasms are addressed. As these questions remain open, examples for detection of well defined "markers" are provided that may be employed as objective criteria for determining clinically important cellular differentiation features.