Impact of Nuclear Interleukin-1 Alpha and EGFR Expression on Recurrence and Survival Outcomes in Oral Squamous Cell Carcinomas.

Interleukin-1 alpha (IL-1 alpha) is a pleiotropic cytokine involved in inflammation and immune response and is upregulated in many solid tumors including head and neck squamous cell carcinomas. Although IL-1 alpha expression is generally associated with poor prognosis, the implications of the subcellular localization of IL-1 alpha expression in patient outcomes are poorly understood. This study is aimed at investigating the prognostic value of nuclear and cytoplasmic immunohistochemical IL-1 alpha expression in oral squamous cell carcinomas (OSCCs). Tissue microarrays containing 146 OSCCs were analyzed for IL-1 alpha and epidermal growth factor receptor (EGFR) expression by immunohistochemistry. IL-1 alpha and EGFR expression scores were correlated with clinicopathological parameters and survival outcomes. IL-1 alpha expression was observed in the nuclear and/or cytoplasmic compartments in 98% of evaluable tumors and 78% of tumors expressed IL-1 alpha in both compartments. There were no differences observed in overall survival or progression-free survival between high, moderate, or negative IL-1 alpha nuclear/cytoplasmic expression scores. When IL-1 alpha nuclear/cytoplasmic expression scores were stratified by positive or negative EGFR expression, tumors with a combined EGFR-positive and high nuclear IL-1 alpha expression profile were significantly more likely to possess perineural invasion and were significantly associated with a high risk of tumor recurrence and worse progression-free survival compared to all other EGFR and combined IL-1 alpha/EGFR expression profiles. Altogether, nuclear IL-1 alpha expression may enhance the prognostic value of EGFR in OSCC and warrants further study as a prognostic biomarker for recurrence.