Tumor budding and complete epithelial mesenchymal transition correlate with late nodal metastasis in early-stage tongue squamous cell carcinoma

Background: Late nodal metastasis is a poor prognostic factor for early-stage tongue squamous cell carcinoma. However, for most early-stage patients, there is a low risk for late nodal metastasis, which currently lacks a diagnostic marker. Tumor budding is a nodal metastasis risk factor in other human cancers. Here, we evaluated tumor budding by partial or complete epithelial-mesenchymal transition and Ovol2 expression, a transcription factor that directly suppresses epithelial-mesenchymal transition. Methods: Sixty-six T1–2N0 patients were enrolled in this retrospective study. Tumor expressions of E-cadherin and vimentin (epithelial-mesenchymal transition markers) and Ovol2 were assessed by immunohistochemistry. Tumor histopathological and immunohistochemical features, mode of invasion, and tumor budding were assessed. Correlations between these potential predictive factors and late nodal metastasis were determined statistically. Results: Univariate analysis demonstrated lymphoid infiltrate, perineural invasion, infiltrative growth pattern, tumor budding, vimentin positive, and complete epithelial-mesenchymal transition were significant factors of late nodal metastasis (all P < 0.05), observed in 25.8 % of patients. Multivariate analysis identified tumor budding and vimentin positive were independent prognostic factors (both P < 0.025). Ovol2 expression was significantly decreased in partial and complete epithelial-mesenchymal transition cells (both P < 0.01) compared with normal epithelia. Univariate analysis, but not multivariate analysis, showed Ovol2 correlated with depth of invasion and tumor budding (both P < 0.05). Conclusion: Tumor budding and vimentin expression are risk factors for late nodal metastasis in T1–2N0 tongue squamous cell carcinoma. Ovol2 might be involved in the early stages of epithelial-mesenchymal transition. Evaluation of these factors might identify patients susceptible to late nodal metastasis who require elective neck dissection.