S100A2, a potential marker for early recurrence in early-stage oral cancer

Early-stage oral cancer patients may have distinct clinical outcomes and respond differently to the same treatment. Up to now, there is still no individual marker to identify such patients with poor outcome. Down-regulation of a tumor suppressor gene, S100A2, in oral cancer cells was identified by mRNA profiling analysis then confirmed by RT-PCR and Southern blotting. The expression of nuclear S100A2 protein examined by immunohistochemistry was not significantly associated with any patient characteristic among the 70 early-stage oral squamous cell carcinoma (SCC) patients. Intriguingly, the loss of nuclear S100A2 positivity was significantly associated with shorter disease-free survival (p = 0.019) while having no effect on the overall survival of these patients. Cox regression analysis with backward elimination identified S100A2 (p = 0.006), tobacco smoking (p = 0.013), and betel quid chewing (p = 0.019) as independent predictors of disease-free survival. This is a first study to demonstrate that loss of nuclear S100A2 may serve as an independent prognostic marker for early-stage oral cancer patients at high risk of recurrence. A more aggressive treatment modality and intensive follow-up may be recommended for the patients with reduced expression of S100A2 in tumor cell nuclei.