Expressão imuno-histoquímica de Histona Desacetilase 6 no processo de carcinogênese bucal experimental em modelo murino

Abstract

Introduction: Oral carcinogenesis is a multifactorial process mediated by genetic and epigenetic alterations. Histone Deacetylase 6 (HDAC6), an enzyme with diverse cytoplasmic functions, has been associated with neoplasm progression, but its expression profile in the sequence from dysplasia to oral carcinoma is not yet fully elucidated. Objective: To analyze HDAC6 immunostaining in normal mucosa, epithelial dysplasia (ED), and oral squamous cell carcinoma (OSCC) in a murine model induced by 4NQO and ethanol, seeking to identify epigenetic markers with diagnostic, prognostic, and therapeutic potential. Materials and Methods: A total of 120 C57BL/6J mice were used, distributed into eight experimental groups according to treatment (4NQO/EtOH, 4NQO/H₂O, PPG/EtOH, PPG/H₂O) and sex. After 25 weeks, the tongues were processed for histopathological analysis (classified as normal mucosa - NM, mild dysplasia - MiD, severe dysplasia - SeD, and squamous cell carcinoma - SCC) and subsequently subjected to immunohistochemistry for HDAC6. Staining quantification was performed by digital morphometry. Results: HDAC6 expression demonstrated a dynamic profile throughout carcinogenesis. In both sexes, a significant increase in immunostaining was observed in dysplastic lesions (MiD and SeD) when compared to SCCs, which exhibited a heterogeneous pattern and lower immunoreactivity. Although trends of variation in expression related to sex and the carcinogenic agent were noted, these differences did not reach statistical significance. Conclusion: HDAC6 shows increased expression in the initial phases of experimental oral carcinogenesis, with a marked reduction in established carcinomas. This pattern suggests a relevant role of the enzyme in the pre-malignant phase, positioning it as a potential marker of interest for future studies on oral tumor progression.