Pathogenesis of Basal Carcinoma and Features of Development of Local Recurrences in Head and Neck. Summary of the Doctoral Thesis

Abstract

Ultraviolet radiation is known to be a major cause of skin malignancies, including basal cell carcinoma (BCC), the most common type of skin cancer. With frequent development in the head and neck region, BCC is characterized by deep tissue invasion and recurrence, therefore, it is important to investigate clinical, dermatoscopic, and morphological criteria for different forms of BCC, as misinterpretation leads to incorrect treatment tactics, aggressive tumour progression, and recurrence. Ultraviolet radiation is not the only predisposing factor, also sunlight is important for general health and vitamin D synthesis in the skin, which deviates from optimal vitamin D levels with a tendency to develop BCC. Previous studies have highlighted the need to systematically evaluate primary and relapsing BCCs based on a better understanding of their morphological structure and the biology of a tumour microenvironment. Accumulating evidence suggests that vitamin D antagonises the transmission of Sonic Hedgehog (SHh) signals, and, therefore, plays an important protective role in BCCs development. The prevalence and characteristics of primary and recurrent head and neck BCCs were assessed in 79 subjects; dermatoscopic criteria were recognized; serum vitamin D levels and vitamin D binding protein (VDBP) expression in BCC tissues were assessed. The essential components of the basement membrane (BM) ‒ type IV collagen and laminin were evaluated immunohistochemically; a tumour cell biology and tumour microenvironment (TME) were explored by studying the expression of alpha-smooth muscle actin (α-SMA), podoplanin (PDPN), and SHh. The most frequent dermatoscopic criteria were established for all types of BCC; the impaired intergrity of the BM in BCC was confirmed; an increase in peritumoural and whole-panstromal α-SMA reactivity was confirmed in mixed and recurrent BCC. A marked increase in the level of SHh expression was observed in the aggressive variants of the BCC ‒ infiltrative, mixed, and micronodular. Vitamin D deficiency was determined in the cohort of patients with both primary and recurrent BCC of the head and neck. There was no statistically significant difference in serum vitamin D levels between men and women. Higher serum vitamin D levels were correlated with the appearance of smaller neoplasms and a more favorable disease prognosis. In smaller tumours with a favorable course, such as superficial and nodular BCC, the association between high-VDBP and low-SHh tissue expression was found, providing supportive evidence of the existence of a link between vitamin D, proteins involved in its metabolism, and SHh signaling pathway.