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SOX2 As a Biomarker of Pathological Response in Oral Cavity Squamous Cell Carcinoma Treated With Neoadjuvant
Aishwarya Sharma1,2, Najinder Preet Kaur1,2, Rasheeda Mohamedali1,2
1Department of Oncopathology, Homi Bhabha Cancer Hospital and Research Centre, New Chandigarh, India.
Background:
Neoadjuvant chemotherapy response is highly variable in locally advanced oral cavity squamous cell carcinoma. SOX2, a stemness-associated transcription factor, promotes chemoresistance through cancer stem cell maintenance. No prior study has evaluated pretreatment SOX2 protein expression as a predictor of pathological response to neoadjuvant chemotherapy in this disease. We present the first retrospective evaluation of this question, assessed against the Hirakawa tumour regression grading system.
Methods:
Fifty-four patients with locally advanced oral cavity squamous cell carcinoma receiving neoadjuvant chemotherapy followed by curative surgery were analysed retrospectively. SOX2 immunohistochemistry was performed on paired pre- and post-treatment specimens in 47 patients, defined as the primary analytic cohort. Pathological response was graded using the Hirakawa tumour regression grading system. Kaplan-Meier and Cox proportional hazards analyses were performed for event-free and overall survival. Subgroup analyses stratified by NACT regimen were additionally performed.
Results:
SOX2 negativity was significantly associated with a favourable pathological response (odds ratio 6.22, 95% confidence interval 1.32-29.29, p = 0.021), with a negative predictive value of 82.4%. This association was directionally consistent across NACT subgroups, which did not differ significantly in pathological response or survival. Good responders demonstrated significantly superior event-free survival (p = 0.006). Nodal metastasis was the dominant independent predictor of event-free survival on multivariate Cox analysis (hazard ratio 6.23, p = 0.026).
Conclusions:
SOX2 negativity at baseline is associated with a favourable neoadjuvant chemotherapy response in locally advanced oral cavity squamous cell carcinoma. The Hirakawa tumour regression grading system demonstrated strong prognostic discrimination for event-free survival. Prospective, externally validated evaluation of SOX2 within a multi-marker prediction panel is warranted; these findings should be regarded as hypothesis-generating pending such validation.