STAT3 Expression in Organ-Preserved Laryngeal Carcinomas: Correlation with Treatment Resistance and Conventional Parameters.

BACKGROUND: One of the major challenges in the treatment of laryngeal squamous cell carcinoma (LSCC) with organ-preserving therapies is the emergence of treatment resistance. The JAK/STAT pathway has been increasingly implicated in this resistance, particularly through the overexpression or persistent activation of STAT3. Increased STAT3 expression is thought to be associated with resistance to radiotherapy and/or chemotherapy, and STAT3 inhibitors have been proposed as potential targeted treatments. OBJECTIVES: The primary objective of this study is to investigate the relationship between STAT3 expression and treatment resistance in patients with LSCC undergoing organ-preserving therapy and to evaluate the association between STAT3 expression and clinical/histopathologic prognostic parameters. A secondary objective is to evaluate STAT3 expression in diagnostic biopsies and laryngectomy specimens from treatment-resistant patients to investigate the potential predictability of treatment resistance from initial biopsy specimens. METHODOLOGY: The study included 123 patients diagnosed with LSCC between 2008 and 2022, all of whom received nonsurgical treatment. Patients were divided into two groups based on their response to treatment: treatment-sensitive patient group (TSPG) and treatment-resistant patient group (TRPG). Immunohistochemical staining for p-STAT3 was performed on a diagnostic biopsy for each TSPG patient and on both pre- and post-treatment biopsies for each TRPG patient. STAT3 expression levels were scored and their association with treatment resistance, clinical and pathological parameters was analysed. RESULTS: No statistically significant difference in p-STAT3 expression was found between the two groups. TSPG patients were significantly older at diagnosis (p = 0.038), and tumor location differed between groups (p = 0.001). No significant differences in histopathologic or clinical prognostic parameters were observed between patients with high and low STAT3 expression. In addition, no significant difference in STAT3 staining was found between diagnostic biopsies and laryngectomy specimens in TRPG patients. CONCLUSION: STAT3 expression was not associated with treatment resistance in LSCC, and its expression level did not correlate with prognostic parameters or survival outcomes. Therefore, STAT3 does not appear to be a useful biomarker for predicting treatment resistance or prognosis in LSCC.