Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons · 2026
Clinicopathological Significance of Interleukin-33 Expression in Squamous Cell Carcinoma of the Lower Lip.
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Arslan İbrahim, Sadullahoğlu Canan, Senirli Rezarta Taga, Yüksel Yeşim, Gür Özer Erdem, Yılmazçoban Hatice
Аннотация
BACKGROUND: Squamous cell carcinoma (SCC) of the lower lip is the most common lip malignancy. Interleukin-33 (IL-33) is an inflammatory cytokine implicated in tumor biology, but its role in lower lip SCC remains unclear.
PURPOSE: To measure the association between IL-33 expression and clinicopathological characteristics and survival outcomes in lower lip SCC.
STUDY DESIGN, SETTING, SAMPLE: Retrospective cohort study at Antalya Education and Research Hospital. Included: patients with lower lip SCC treated surgically between 2017 and 2022. Excluded: positive surgical margins, prior chemotherapy or radiotherapy, second primary tumors, and distant metastasis at diagnosis.
PREDICTOR VARIABLE: Nuclear IL-33 expression categorized as positive (>20% of tumor cells showing nuclear staining) or negative (≤20%).
MAIN OUTCOME VARIABLE(S): Primary outcome: overall survival (OS).
SECONDARY OUTCOME: local recurrence (LR).
COVARIATES: Demographic variables included age and sex. Tumor-related variables included tumor stage, nodal stage, histological grade, and depth of invasion (DOI).
ANALYSES: Pearson χ2 and Fisher's exact tests for categorical variables; Mann-Whitney U test for DOI. Survival analyses: Kaplan-Meier with log-rank test and Cox proportional hazards regression. A P value < .05 considered statistically significant.
RESULTS: The study sample was composed of 76 subjects with a mean age of 71.1 (standard deviation, 13.4) years; 19 subjects (25.0%) were female and 57 (75.0%) were male. Median follow-up was 60 months (interquartile range, 25 to 84). The estimated 5-year OS rate was 58.5%. The estimated 5-year OS rates were 68.6 and 50.5% in the IL-33-positive and IL-33-negative groups, respectively, with no statistically significant difference (log-rank P = .1). IL-33 expression was statistically significantly associated with LR; recurrence occurred in 21.3% of IL-33-negative patients and in none of the IL-33-positive patients (P = .01). Patients with IL-33-positive tumors had statistically significantly better LR-free survival (log-rank P = .01). In multivariable analysis, age >70 years (P = .001) and increasing DOI (P = .003) were independently associated with OS.
CONCLUSIONS AND RELEVANCE: IL-33 expression was not statistically significantly associated with OS in patients with SCC of the lower lip. However, IL-33 expression was associated with earlier T stage, lower DOI, and better LR-free survival, suggesting a potential association with less-aggressive tumor behavior.
PURPOSE: To measure the association between IL-33 expression and clinicopathological characteristics and survival outcomes in lower lip SCC.
STUDY DESIGN, SETTING, SAMPLE: Retrospective cohort study at Antalya Education and Research Hospital. Included: patients with lower lip SCC treated surgically between 2017 and 2022. Excluded: positive surgical margins, prior chemotherapy or radiotherapy, second primary tumors, and distant metastasis at diagnosis.
PREDICTOR VARIABLE: Nuclear IL-33 expression categorized as positive (>20% of tumor cells showing nuclear staining) or negative (≤20%).
MAIN OUTCOME VARIABLE(S): Primary outcome: overall survival (OS).
SECONDARY OUTCOME: local recurrence (LR).
COVARIATES: Demographic variables included age and sex. Tumor-related variables included tumor stage, nodal stage, histological grade, and depth of invasion (DOI).
ANALYSES: Pearson χ2 and Fisher's exact tests for categorical variables; Mann-Whitney U test for DOI. Survival analyses: Kaplan-Meier with log-rank test and Cox proportional hazards regression. A P value < .05 considered statistically significant.
RESULTS: The study sample was composed of 76 subjects with a mean age of 71.1 (standard deviation, 13.4) years; 19 subjects (25.0%) were female and 57 (75.0%) were male. Median follow-up was 60 months (interquartile range, 25 to 84). The estimated 5-year OS rate was 58.5%. The estimated 5-year OS rates were 68.6 and 50.5% in the IL-33-positive and IL-33-negative groups, respectively, with no statistically significant difference (log-rank P = .1). IL-33 expression was statistically significantly associated with LR; recurrence occurred in 21.3% of IL-33-negative patients and in none of the IL-33-positive patients (P = .01). Patients with IL-33-positive tumors had statistically significantly better LR-free survival (log-rank P = .01). In multivariable analysis, age >70 years (P = .001) and increasing DOI (P = .003) were independently associated with OS.
CONCLUSIONS AND RELEVANCE: IL-33 expression was not statistically significantly associated with OS in patients with SCC of the lower lip. However, IL-33 expression was associated with earlier T stage, lower DOI, and better LR-free survival, suggesting a potential association with less-aggressive tumor behavior.