Modern view on epidermal dysplasia carcinogenesis
Authors: Oshyvalova O. , Rossokha Z. 
Published: October 2019

Summary. Squamous cell carcinoma of the skin develops from the spectrum of facultative precancerous conditions, which in the course of malignant transformation through cancer stage in situ without early treatment fully transform into invasive squamous cell carcinoma. According to classical model of carcinogenesis, the transformation of actinic keratosis into squamous cell carcinoma of the skin occurs due to a mutation in one gene, more often a tumor suppressor, and undergoes a stage of development with lack of control of cell cycle. The aim of the research is to supplement current knowledge of genetic determination of pathogenetic mechanisms of epidermal dysplasia of the skin by studying the genetic determinant in the skin lesion of varying degrees of malignancy. Materials and Methods: We analyzed 85 skin bioptates of patients with epidermal dysplasia of the skin (Gr 1 — 43 patients with actinic keratosis; Gr 2 — 21 patients with non-invasive squamous cell carcinoma of the skin; Gr 3 — 21 patients with invasive squamous cell carcinoma of the skin) by molecular genetic testing of gene polymorphisms: TP53 (G13494A), L-myc (T3109G), TNF-α (G308A) in tumor tissue. The histological examination revealed the levels of dysplasia of the epidermis. Results: In case of the same disease duration in patients of Gr1/Gr3, L-myc (3109TT) is a genetic component of malignant transformation of epithelial skin cells (p = 0.004) and the development of invasive squamous cell carcinoma. Other variants of 3109TG and 3109GG genes do not have such prognostic value for the risk of skin cancer compared to 3109TT. Significant differences were found in the distribution of (13494GA) when comparing Gr 1 with Gr 3 (p = 0.014) and Gr 2 with Gr 3 (p = 0.038). A significant increase in the distribution of 13494GA genotype was revealed in patients with invasive form of keratinocyte intraepidermal neoplasia. 13494A allele was more likely to be detected in patients of Gr 3 compared to Gr 2 (p = 0.030) that proves the association of this allele with the development of invasive malignancies of the skin. The association of 308GG genotype and TNF-α (308G) allele with the development of malignant skin lesions was found. Comparing the distribution of 308G allele in patients of Gr 1 and Gr 2, we found its significant increase in patients of Gr 1. Comparative analysis of gene polymorphism with tumor invasion level showed a significant difference only in 308GG genotype between patients with grade III of KIN (keratinocyte intraepidermal neoplasia) in Gr 2 and patients with KIN III of Gr 1 (p = 0.007), and 308GA between patients with KIN III of Gr 2 and KIN III of Gr 1 (p = 0.027). Conclusions. Our work has supplemented modern vision of genetic component in pathogenetic mechanism of the development of epidermal dysplasia of the skin. Thus, the association of L-myc (3109TT) with the development of malignant skin lesions of different invasiveness and the modifying effect of TNF-α (G308A) and TP53 (G13494A) gene variants on pathological transformation in the focus of EDS depending on the level of epithelial dysplasia was revealed.