Increased epidermal thickness and abnormal epidermal differentiation in keloid scars

Summary Background The pathogenesis underlying keloid formation is still poorly understood. Research has focused mostly on dermal abnormalities, while the epidermis has not yet been studied. Objectives To identify differences within the epidermis of mature keloid scars compared with normal skin and mature normotrophic and hypertrophic scars. Methods Rete ridge formation and epidermal thickness were evaluated in tissue sections. Epidermal proliferation was assessed using immunohistochemistry (Ki67, keratins 6, 16 and 17) and with an in vitro proliferation assay. Epidermal differentiation was evaluated using immunohistochemistry (keratin 10, involucrin, loricrin, filaggrin, SPRR2, SKALP), reverse‐transcriptase polymerase chain reaction (involucrin) and transmission electron microscopy (stratum corneum). Results All scars showed flattening of the epidermis. A trend of increasing epidermal thickness correlating to increasing scar abnormality was observed when comparing normal skin, normotrophic scars, hypertrophic scars and keloids. No difference in epidermal proliferation was observed. Only the early differentiation marker involucrin showed abnormal expression in scars. Involucrin was restricted to the granular layer in healthy skin, but showed panepidermal expression in keloids. Normotrophic scars expressed involucrin in the granular and upper spinous layers, while hypertrophic scars resembled normotrophic scars or keloids. Abnormal differentiation was associated with ultrastructural disorganization of the stratum corneum in keloids compared with normal skin. Conclusions Keloids showed increased epidermal thickness compared with normal skin and normotrophic and hypertrophic scars. This was not due to hyperproliferation, but possibly caused by abnormal early terminal differentiation, which affects stratum corneum formation. Our findings indicate that the epidermis is associated with keloid pathogenesis and identify involucrin as a potential diagnostic marker for abnormal scarring. What's already known about this topic? With regards to keloid scarring, the focus has always been on the dermal compartment when studying the underlying pathogenesis. However, we know that epidermal–dermal interactions are essential in wound healing and, as such, the epidermis of keloid scars is worth further investigation. While epidermal abnormalities have already been described in hypertrophic scars, the literature on the keloid epidermis remains inconclusive. What does this stud