Hypertrophic scarring is associated with epidermal abnormalities: an immunohistochemical study

The role of epidermal keratinocytes in the early phases of normal unimpaired wound healing has been studied extensively. However, little is known about the cell biological processes in the epidermis and the basal membrane zone during the later phases of dermal matrix formation and remodelling of the scar tissue. This study investigated epidermal growth and differentiation and maturation of the basal membrane zone. Biopsies were taken from (clinically) hypertrophic and non-hypertrophic scars at 3 and 12 months after a breast-reduction operation. Tissues were analysed using immunohistochemical techniques. The data showed that epidermal abnormalities with respect to differentiation persist up to 3 months, as witnessed by the expression of cytokeratin 16. Remarkably, hypertrophic scars that remained hypertrophic throughout the period of analysis (up to 12 months) showed significantly more cytokeratin 16 expression at 3 months, when compared either with normal scars or with hypertrophic scars that became normal after 12 months. Staining for Ki-67 antigen, a marker for cell proliferation, revealed an increase in basal keratinocyte proliferation rate in 3-month-old hypertrophic scars compared with non-hypertrophic scars. After 12 months, this difference had disappeared completely and the number of cycling basal cells had returned to normal values. Three-month-old hypertrophic scars showed more acanthosis than non-hypertrophic scars of the same age, irrespective of whether they remained hypertrophic or became normal scars. After 12 months, this difference was no longer present. Staining for various heparan sulphate proteoglycan epitopes revealed that restoration of the basal membrane was incomplete at 3 months, but was complete at 12 months with respect to this component. No differences in the expression of several components of the basal membrane zone (heparan sulphate proteoglycan, laminin, tenascin) were noted between hypertrophic and non-hypertrophic scars. These data show that in the early phase of hypertrophic scarring, epidermal abnormalities are found compared with normal wound healing. In addition, early (3 months) epidermal abnormalities are associated with the clinical outcome at 12 months. These findings raise the possibility that the epidermal compartment is involved in the pathogenic process.