STAT3 Expression in Organ-Preserved Laryngeal Carcinomas: Correlation with Treatment Resistance and Conventional
Esra Nur Bayır1,2, Ünsal Han3, Ömer Bayır4
1Ankara Etlik City Hospital, Department of Pathology, Ankara, Türkiye. esranrbyr@gmail.com.
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.
Insights
STAT3 expression did not predict treatment resistance in laryngeal squamous cell carcinoma (LSCC) patients undergoing organ-preserving therapy. This finding suggests STAT3 is not a reliable biomarker for treatment outcomes in LSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Treatment resistance in laryngeal squamous cell carcinoma (LSCC) is a significant clinical challenge.
- The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, particularly STAT3, is implicated in therapeutic resistance.
- STAT3 inhibitors are being explored as potential targeted therapies for LSCC.
Purpose of the Study:
- To investigate the association between STAT3 expression and treatment resistance in LSCC patients receiving organ-preserving therapy.
- To evaluate the correlation of STAT3 expression with clinical and histopathologic prognostic parameters.
- To assess the predictive value of STAT3 expression in diagnostic biopsies for treatment resistance.
Main Methods:
- 123 LSCC patients treated nonsurgically between 2008 and 2022 were analyzed.
- Patients were categorized into treatment-sensitive and treatment-resistant groups.
- Immunohistochemical staining for phosphorylated STAT3 (p-STAT3) was performed on biopsy specimens; expression levels were correlated with clinical data.
Main Results:
- No statistically significant difference in p-STAT3 expression was observed between treatment-sensitive and treatment-resistant patient groups.
- STAT3 expression levels did not correlate with histopathologic or clinical prognostic parameters.
- STAT3 staining in diagnostic biopsies showed no significant difference compared to laryngectomy specimens in resistant cases.
Conclusions:
- STAT3 expression is not associated with treatment resistance in LSCC.
- STAT3 levels do not appear to be a useful biomarker for predicting treatment resistance or prognosis in LSCC patients.
- Further research may explore alternative biomarkers for predicting treatment response in LSCC.
