Immunohistochemical evaluation of SOX9 expression in oral squamous cell carcinoma, pharyngeal and thyroid carcinomas

Head and neck squamous cell carcinoma (HNSCC) remains a major global health challenge with significant morbidity and mortality. While SOX9, a key transcription factor, has been implicated in cancer stem cell biology and treatment resistance, its expression patterns across different head and neck malignancies remain incompletely documented. Hence, the present study aimed to evaluate SOX9 expression across oral squamous cell carcinoma (OSCC), pharyngeal carcinoma, and thyroid carcinoma.

A retrospective immunohistochemical analysis was performed on 90 tissue specimens (30 cases each of OSCC, pharyngeal carcinoma, and thyroid carcinoma). SOX9 expression was assessed for staining percentage, intensity, and subcellular localisation by two independent pathologists. Statistical analyses was performed using Chi-square and Kruskal-Wallis tests (P < 0.05).

Thyroid carcinoma exhibited the highest SOX9 expression, with 60% showing 76-100% positivity versus 13.3% in OSCC and 23.3% in pharyngeal carcinoma (P = 0.001). Mean rank analysis confirmed significant differences (χ² = 21.674, P < 0.001). In OSCC and pharyngeal carcinoma, SOX9 expression correlated positively with tumour grade (r = 0.665 and r = 0.512, respectively, P < 0.01), while thyroid carcinoma showed no such correlation. Nuclear localisation predominated across all groups (83.3-93.3%, P = 0.477).

The present study shows that SOX9 behaves differently across head and neck cancers rising with tumour grade in squamous cell carcinomas but showing an inverse pattern in thyroid cancers, where high expression indicates well-differentiated tumours and decreases with dedifferentiation. These contrasting patterns suggest SOX9 could be a useful diagnostic and prognostic marker whose significance depends on cancer type.