Learning Objectives: To understand the processes involved differentiation of normal stratified squamous epithelia To understand the changes in keratinocte hyperproliferation, dysplasia and structural genodermatoses.
The biology of the keratinocyte has been greatly enlightened by the ability to culture keratinocytes from the epidermis and mucosal stratified squamous epithelia in the laboratory, developed in 1975 by the use of a feeder layer and added growth factors. Subsequently the processes regulating keratinocyte stratification and diffentiation have been characterised, in particular the changes in keratin expression, as a cell migrates from the stem cell compartment within the basal layer into suprabasal layers , and the formation of the cornified envelope. Normal site specific differentiation is heavily dependent on both permissive and directive signals from the underlying dermis. During hyperplasia, as seen in the skin during psoriasis and wound healing, the keratinocyte undergoes an alternative pathway of differentiation with alterations in keratin expression particularly keratins 6 and 16 and additional effects on terminal differentation. In dysplasia and malignancy, markers of keratinocyte differentiation tend to remain but additional expression of simple epithelial markers is associated with tumour invasion. Many genetically inherited skin diseases and associated syndromes, such as sensorineural deafness, are associated with point mutations in structural proteins including keratins, and junctional complexes. Patients with atopic eczema has been found the have a very rate of mutations in filaggrin: a filament aggregating protein critical for formation of a normal stratum corneum and these mutations result in significant impairment of barrier function, a hallmark of atopic eczema. Understanding keratinocyte differentiation and alterations in disease can give insights into the pathology of other stratified squamous epithelia including cholesteatoma.
