α-Smooth muscle actin-positive myofibroblasts, in association with epithelial-mesenchymal transition and lymphogenesis, is a critical prognostic parameter in patients with oral tongue squamous cell carcinoma

Abstract

Background: α-Smooth muscle actin (α-SMA)-positive myofibroblasts play a pivotal role in progression and metastasis of solid carcinomas. Epithelial-mesenchymal transition (EMT) of cancer cells and lymphogenesis of tumor microenvironment are the important events in tumor metastasis. This study aimed to investigate the relationship between the expression of myofibroblasts marker, α-SMA, and clinicopathological features, EMT, lymphogenesis, and prognostic status in oral tongue squamous cell carcinoma (OTSCC).

Methods: Immunohistochemisty was used to detect α-SMA expression in 50 OTSCCs. EMT and lymphogenesis were also identified by immunostaining with N-cadherin, vimentin, and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1).

Results: There was a significant correlation respectively between the α-SMA (P = 0.002), vimentin (P < 0.001), N-cadherin (P = 0.025) expression and cervical lymph node metastasis of OTSCC. Carcinomas with α-SMA (P = 0.001), vimentin (P = 0.003), and N-cadherin (P = 0.012) expression were more advanced in terms of tumor-node-metastases status. Univariate analysis showed that pathologic node status (P < 0.001), α-SMA (P = 0.001), and vimentin expression (P = 0.044) was significantly associated with overall survival time, but multivariate analysis just showed the α-SMA expression (P = 0.008) and pathologic node status (P = 0.003) was independently predictive of prognosis. Furthermore, statistical analysis showed significant correlation between α-SMA expression and vimentin (P = 0.037), N-cadherin (P = 0.019), or LYVE-1 positive vessel count (P = 0.041).

Conclusion: Our results indicate that α-SMA-positive myofibroblasts have important impacts on cancer progression, metastasis, and survival prognosis of patients with OTSCC. The functions of α-SMA-positive myofibroblasts in OTSCC may be associated with promoting EMT of tumor cells and lymphogenesis of metastasis microenvironment.

Keywords: epithelial-mesenchymal transition; lymphogenesis; myofibroblasts; oral tongue squamous cell carcinoma; prognosis.