Features of Neural Microenvironment Remodelling in cervical intraepithelial neoplasia and squamous Cell Carcinoma
Despite the central role of epithelial dysplasia and HPV infection in cervical carcinogenesis, changes in the stromal microenvironment and neural remodelling remain the least studied areas. Our study examines the distribution and structural changes of peripheral nerve fibres across the spectrum of cervical intraepithelial neoplasia and invasive squamous cell carcinoma. Forty-five cervical tissue samples (9 normal, CIN1, CIN2, CIN3, and SCC) were stained using antibodies to PGP9.5, S100, CD56, and CD34. The density, maximum diameter, and distance from the epithelial basement membrane of nerve fibres were quantified. S100 and CD56 expression were semiquantitatively assessed. A progressive increase in PGP9.5-positive nerve fibres was observed from CIN1 to SCC, which was also accompanied by an increase in nerve fibre diameter. Hypertrophy of nerve fibres progressively increases with increasing dysplasia. Some fibres are normal, while others are neurogenic fibres resulting from neoangiogenesis. In CIN3 and SCC, NK (natural killer cells) are sharply reduced, which is explained by the presence of neoneurogenic fibres that dominate at this stage. Initially, in cases of low-grade dysplasia, NK cell hyperplasia increases along with hypertrophy, although its number is minimal in CIN3 and SCC. This may represent a manifestation of escape from neuroregulation/tumour escape from the immune system. These results may be used to refine immunotherapy better and develop NK-targeted drugs.
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