Retinoic acid receptor-alpha as a prognostic indicator in oral squamous cell carcinoma

Retinoids reverse potentially malignant lesions and inhibit the development of second primary tumors in oral cancer patients by binding to nuclear retinoid receptors. Alterations in the expression of retinoid receptor-alpha are implicated in tumor progression. Herein, we hypothesized that increased expression of RARalpha protein in oral squamous cell carcinoma (SCC) is associated with a poor clinical outcome and thus may serve as a prognostic factor. Retrospective immunohistochemical analysis of RARalpha protein expression was carried out in paraffin-embedded tissue sections from 115 patients with completely resected oral SCCs for whom clinical follow-up data were available. Increased expression of RARalpha protein was observed in 67/115 (58%) oral SCCs (weakly positive in 38 patients and strongly positive in 29 patients). Kaplan-Meier analysis showed that patients with RARalpha positivity had significantly shorter disease-free survival time (median time 40 months vs. 86 months, p = 0.0229). Furthermore, disease-free survival time of the 29 patients with strongly positive RARalpha was significantly worse than for the 86 patients with weak or undetectable levels of RARalpha (p = 0.0328). Strong RARalpha expression in oral SCCs was associated with a significantly worse disease-free survival, suggesting that RARalpha may serve as a prognostic indicator of poor clinical outcome. Further studies are warranted to determine its utility in identifying the subset of patients who would benefit from use of retinoids as adjuvant in chemotherapy or chemopreventive approaches.