PREMALIGNANT LESIONS OF THE UPPER AERODIGESTIVE TRACT - BIOMARKERS OFGENETIC ALTERATIONS, PROLIFERATION, AND DIFFERENTIATION

The normal distribution of cell division in squamous mucosa is in the basal or adjacent suprabasal cell layers. Migration of cells toward th e epithelial surface results in cell differentiation, most often expre ssed by high molecular weight keratin intermediate filaments and compo nents of the cornified envelope, including ''involucrin.'' These latte r expressions of terminal differentiation are common in keratinizing d ysplasia and invasive squamous cell carcinomas. However, they are less common in the non-keratinizing dysplasias, which fail to express evid ence of epithelial maturation. Cell proliferation occurs in or near th e basal layer in normal or reactive/reversible hyperplasias. In dyspla sia (both keratinizing and non-keratinizing), cell proliferation is ob served at all levels of the epithelium. Concomitant with these abnorma lities in proliferation and differentiation are nuclear changes charac terized by large hyperchromatic nuclei. The enlarged nuclei reflect in creased DNA content, as documented by flow cytometry and image analysi s techniques. DNA aneuploidy represents a spectrum of genomic alterati ons reflecting steps toward the progression to invasive carcinoma, whi ch for the most part, have not yet been identified. (C) 1993 Wiley-Lis s, Inc.