G C Limandjaja1, L J van den Broek1, T Waaijman1, H A van Veen2, V Everts2,3, S Monstrey4, R J Scheper5, F B Niessen6, S Gibbs1,3. 1. Department of Dermatology, VU Medical Centre, Amsterdam, the Netherlands. 2. Van Leeuwenhoek Centre for Advanced Microscopy, Amsterdam Medical Centre, Amsterdam, the Netherlands. 3. Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University, Amsterdam, the Netherlands. 4. Department of Plastic Surgery, University of Ghent, Ghent, Belgium. 5. Department of Pathology, VU Medical Centre, Amsterdam, the Netherlands. 6. Department of Plastic, Reconstructive and Hand Surgery, VU Medical Centre, Amsterdam, the Netherlands.
Abstract
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.
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.
Authors: Lohrasb R Sayadi; Rebecca Rowland; Alexandra Naides; Luke Tomlinson; Adrien Ponticorvo; Anthony J Durkin; Alan D Widgerow Journal: Ann Plast Surg Date: 2021-10-01 Impact factor: 1.763
Authors: Lyn M Wise; Christa J Bodaan; Gabriella S Stuart; Nicola C Real; Zabeen Lateef; Andrew A Mercer; Christopher B Riley; Christine L Theoret Journal: PLoS One Date: 2018-05-15 Impact factor: 3.240
Authors: Grace C Limandjaja; Leonarda J van den Broek; Taco Waaijman; Melanie Breetveld; Stan Monstrey; Rik J Scheper; Frank B Niessen; Susan Gibbs Journal: Arch Dermatol Res Date: 2018-10-28 Impact factor: 3.017