Heterogeneity: epidermal morphology and expression of epithelial-mesenchymal transition-related factors between the center and margin of keloids

Abstract

Objective To investigate the causes of keloid invasive growth by comparing the expressional differences of E-cadherin, vimentin, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1α), and the epidermal histological differences among keloid marginal region, central region and normal skin. Methods This study enrolled 16 patients undergoing keloid resection in our department from October 2019 to August 2020, with a total of 16 keloid tissues, and 9 patients who required partial normal skin resection during the operation, with a total of 9 normal skin tissues. Hematoxylin and eosin (H&E) staining was used to observe the tissue morphology, and immunohistochemical staining and Western blot assay were used to detect the expression of E-cadherin, vimentin, VEGF and HIF-1α in above tissues. Results There was obvious abnormality and heterogeneity in the epidermal layer of keloids. The marginal epidermal subdivided into fine-branch-like and then clearly penetrated into the dermis, forming a houndstooth-like appearance, while the central epidermal became thick and flat; Immunohistochemical staining and Western blot assay showed that the expression level of E-cadherin was significantly weaker in the marginal and central epidermal of keloid tissue than in the normal skin (P < 0.05), with that in the margin weaker than the center (P < 0.05); The levels of vimentin, HIF-1α and VEGF were significantly higher in the keloid tissue than normal skin (P < 0.05), and those in the margin took the highest (P < 0.05). Conclusion Marginal epidermis of keloid clearly extends to the dermis in branched appearance, with active epithelium-to-mesenchymal transition (EMT), highly expressed HIF-1α, VEGF and abundant microvessels. The underlying mechanism may be related to the aggressive growth of the keloid edge, and HIF-1α might be the key factor.

Keywords

• keloid
• epidermis
• epithelium-to-mesenchymal transition
• hypoxia-inducible factor-1α