Dynamic transition of pSTAT3 expression demonstrates the highest level in severe oral epithelial dysplasia before downregulation in invasive carcinoma

Abstract

ThailandThis study aimed to preliminarily evaluate the expression of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) in comparison with normal oral mucosa (NOM). Additionally, its potential involvement in the sequential process of oral carcinogenesis was investigated. This study included 75 formalin-fixed, paraffin-embedded tissue specimens, comprising 15 cases each of NOM, mild OED, moderate OED, severe OED, and OSCC. Immunohistochemical analysis was performed to evaluate protein expression. The proportion of positive cells and the staining intensity were semi-quantitatively assessed and recorded as an immunoreactive score (IRS). Comparisons of IRS were conducted among the NOM group, the various grades of OED, and the OSCC group using appropriate statistical analyses. pSTAT3 was found predominantly in the nuclei of epithelial cells, with mild cytoplasmic staining observed to a lesser extent. Immunostaining demonstrated a progressive expansion of positivity from the basal layers in NOM to the superficial epithelial layers in severe OED. Based on the IRS, pSTAT3 expression gradually increased from NOM through the OED groups and declined in the OSCC group. The highest IRS was observed in severe OED compared with NOM (p = 0.002). However, pSTAT3 levels significantly decreased in OSCC compared with severe OED (p = 0.007). pSTAT3 expression progressively increases from NOM to OED, with expansion from basal to full epithelial thickness as the severity of dysplasia increases. These results imply a role of pSTAT3 in early oral carcinogenesis.