Markers of Keratinocyte Differentiation in Preneoplastic and Neoplastic Lesions

In the last few years several laboratories have studied extensively the molecular events leading to the terminal differentiation of squamous epithelia. These studies have shown that the maturation of those stratified epithelia, also known as epidermoid or malpighian, is the result of a coordinated sequence of events that begins with cellular proliferation in the basal or germinative layer (1). The new cells are dislodged from the basal layer and, as they lose contact with the basement membrane, start synthesizing high-molecular-weight keratins (2) and other proteins unrelated to keratins that, in a later step of maturation, are cross-linked, forming a chemical-resistant envelope under the cell membrane (3). Simultaneously the keratins become stabilized by S-S bonds (2) and are organized into bundles of fibers, apparently by a basic protein of the matrix called filaggrin (4). At the same time, modified lysosomal bodies (membrane-coating granules or Odland bodies) secrete their products into the intercellular space, forming an impermeable lipid seal in the superficial epithelial layers, where most of the cellular organelles are lost by an unknown mechanism (5). All these events lead to the formation of a corneocyte, which is located at the most superficial layer of the epithelium, formed mainly from bundles of tonofilaments (keratins) embedded in an amorphous matrix (mainly filaggrin), and surrounded by a cell membrane under which a resistant envelope has been formed (1).